Major Randomized Controlled Trials Research Articles

Treatment for intracerebral hemorrhage: Dawn of a new era.

Intracerebral hemorrhage (ICH) is a devastating disease, causing high rates of death, disability, and suffering across the world. For decades, its treatment has been shrouded by the lack of reliable evidence, and consequently, the presumption that an effective treatment is unlikely to be found. Neutral results arising from several major randomized controlled trials had established a negative spirit within and outside the stroke community. Frustration among researchers and a sense of nihilism in clinicians has created the general perception that patients presenting with ICH have a poor prognosis irrespective of them receiving any form of active management. All this changed in 2023 with the positive results on the primary outcome in randomized controlled trials showing treatment benefits for a hyperacute care bundle approach (INTERACT3), early minimal invasive hematoma evacuation (ENRICH), and use of factor Xa-inhibitor anticoagulation reversal with andexanet alfa (ANNEXa-I). These advances have now been extended in 2024 by confirmation that intensive blood pressure lowering initiated within the first few hours of the onset of symptoms can substantially improve outcome in ICH (INTERACT4) and that decompressive hemicraniectomy is a viable treatment strategy in patients with large deep ICH (SWITCH). This evidence will spearhead a change in the perception of ICH, to revolutionize the care of these patients to ultimately improve their outcomes. We review these and other recent developments in the hyperacute management of ICH. We summarize the results of randomized controlled trials and discuss related original research papers published in this issue of the International Journal of Stroke. These exciting advances demonstrate how we are now at the dawn of a new, exciting, and brighter era of ICH management.

Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT. Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT. Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up. Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.

A rare case of a pharyngeal-cervical- brachial variant of Guillain–Barré syndrome

Abstract: Guillain–Barre syndrome (GBS) is an acute, usually symmetrical, and typically de myelinating polyneuropathy, characterized by progressive, ascending paralysis and areflexia, with or without abnormal sensory function. Therapeutic plasma exchange(TPE) was the first therapeutic modality to impact the disease favorably, and several major randomized controlled trials (RCTs) have confirmed its efficacy. Our case is unique, as this critically ill patient admitted in the intensive care unit (ICU), developed a rare form of GBS, the PCB variant of the disease, and was successfully treated with TPE. The diagnosis of PCB can be challenging due to atypical clinical features but its unique presentation does provide sufficient clues to narrow the differential diagnosis, which is helpful in starting empirical therapy at the earliest. Immunomodulation with plasma exchange and IVIG have been found to improve treatment outcomes; 70%–80% of patients usually have a complete recovery. Early diagnosis is very important in the case of the PCB variant of GBS to enable timely intervention. Diagnosis can be made on history and neurological findings alone.

Generalizability of Randomized Clinical Trial Outcomes for Diabetes Control Resulting From Bariatric Surgery

Objective: To assess the external validity of randomized controlled trials (RCTs) of bariatric surgical treatment on diabetes control. Background: Multisite RCTs provide the strongest evidence supporting clinical treatments and have the greatest internal validity. However, characteristics of trial participants may not be representative of patients receiving treatment in the real world. There is a need to assess how the results of RCTs generalize to all contemporary patient populations undergoing treatments. Methods: All patients undergoing sleeve gastrectomy at University of California Los Angeles (UCLA) between January 8, 2018 and May 19, 2023 had their baseline characteristics, weight change, and diabetes control compared with those enrolled in the surgical treatment and medications potentially eradicate diabetes efficiently (STAMPEDE) and diabetes surgery study (DSS) RCTs of bariatric surgery’s effect on diabetes control. Weight loss and diabetes control were compared between UCLA patients who did and did not fit the entry criteria for these RCTs. Results: Only 65 (17%) of 387 patients with diabetes fulfilled the eligibility criteria for STAMPEDE, and 29 (7.5%) fulfilled the criteria for DSS due to being older, having higher body mass index, and lower HbA1c. UCLA patients experienced slightly less weight loss than patients in the RCTs but had similar diabetes control. The 313 (81%) patients not eligible for study entry into either RCT had similar long-term diabetes control as those who were eligible for the RCTs. Conclusions: Even though only a very small proportion of patients undergoing bariatric surgery met the eligibility criteria for the 2 major RCTs, most patients in this contemporary cohort had similar outcomes. Diabetes outcomes from STAMPEDE and DSS generalize to most patients undergoing bariatric surgery for diabetes control.

Comparing the efficacy of vedolizumab between males and females: a post-hoc analysis of GEMINI-1 and VARSITY.

Vedolizumab is a first-line treatment option for ulcerative colitis. There are differences in incidence of ulcerative colitis between males and females, but whether sex affects treatment outcomes is less clear. We examined sex-based differences in patients with ulcerative colitis initiated on vedolizumab from two major randomized controlled trials (RCTs). We conducted a post-hoc analysis on participants with ulcerative colitis from the VARSITY and GEMINI-1 RCTs who received vedolizumab. Outcomes of interest were rates of clinical improvement, clinical remission, and endoscopic improvement at weeks 6, 14, and 52 in male and female participants, as were differences in concentrations of trough vedolizumab and C-reactive protein; 1009 persons in GEMINI-1 and VARSITY trials were included. Male and female patients had similar disease characteristics aside from males being more likely to have Mayo 3 grade endoscopic severity at baseline (62.8 vs. 48.9%, P < 0.001). At week 6, females were more likely to have endoscopic improvement (47.4 vs. 35.2%, P = 0.001) and increased vedolizumab trough levels [34.0 (23.0-44.5) vs. 28.9 (19.0-34.6), P < 0.001]. The probability of achieving clinical remission (28.9 vs. 34.5%, P = 0.057) or endoscopic improvement (35.5 vs. 39.3%, P = 0.212) at week 52 was not different between males and females. Females with ulcerative colitis treated with vedolizumab appear more likely to achieve early endoscopic improvement than males, though longer-term outcomes demonstrated no difference. Further studies are required to better understand mechanisms through which sex or sex-associated factors could influence response to therapy in ulcerative colitis.

Atrial Fibrillation Detection and Load: Knowledge Gaps Related to Stroke Prevention.

Atrial fibrillation is a major cause of ischemic stroke. Technological advances now support prolonged cardiac rhythm monitoring using either surface electrodes or insertable cardiac monitors. Four major randomized controlled trials show that prolonged cardiac monitoring detects subclinical paroxysmal atrial fibrillation in 9% to 16% of patients with ischemic stroke, including in patients with potential alternative causes such as large artery disease or small vessel occlusion; however, the optimal monitoring strategy, including the target patient population and the monitoring device (whether to use an event monitor, insertable cardiac monitor, or stepped approach) has not been well defined. Furthermore, the clinical significance of very short duration paroxysmal atrial fibrillation remains controversial. The relevance of the duration of monitoring, burden of device-detected atrial fibrillation, and its proximity to the acute ischemic stroke will require more research to define the most effective methods for stroke prevention in this patient population.

Editor's Choice – RANDOMisation Screening for Drug coated or Drug Eluting Device Randomised Trials Among Patients Undergoing Endovascular FemorOPopliteal Procedures (RANDOM-STOP study)

The aim was to assess the proportion of patients undergoing endovascular therapy for femoropopliteal arterial disease (FP) who would be eligible to take part in seven major randomised controlled trials (RCTs) that investigated the efficacy of some of the currently available paclitaxel based (PTX) devices used in this clinical context. Various RCTs have shown a potential clinical benefit from the use of paclitaxel in FP endovascular therapy. Nonetheless, patients enrolled were highly selected and the generalisability of these findings in pragmatic cohorts is unclear. Between 1 January and 31 December 2021, all consecutive patients who underwent endovascular procedures for symptomatic FP disease in 16 European centres were retrospectively screened and included in this analysis. The primary outcome measure was individual patient eligibility for inclusion into at least one of the seven RCTs. The reasons for exclusion (clinical and or radiological) as well as in hospital death and morbidity were also reported. A total of 1 567 consecutive patients (959 male, 61%), corresponding to 1 567 lower limbs, were included. Most patients (1 009 patients, 64.39%) were treated for chronic limb threatening ischaemia (CLTI). A total 1 280 patients (81.68%) were not eligible for inclusion in any of the evaluated RCTs. Of them, 741 (47.28%) were excluded for clinical and 1 125 (71.79%) for radiological reasons. The analysed RCTs assessing the efficacy or effectiveness of PTX based endovascular therapies do not seem representative of the patient population with FP disease receiving endovascular therapy in routine clinical practice.

The Wedding Bells Sound Really Good! iGlarLixi Fixed-Ratio Combination in the Treatment of Type2 Diabetes: A Narrative Review.

iGlarLixi is a fixed-ratio combination of insulin glargine 100U/mL and lixisenatide used in the treatment of type2 diabetes. iGlarLixi has proven clinical benefits in terms of glycemia, weight control, and safety, defined by the risk of hypoglycemia. It simultaneously targets many pathophysiologic abnormalities which are at the root of type2 diabetes and thus presents a complementary mode of action. Finally, it may also address diabetes treatment burden, and, by decreasing the complexity of treatment, it may improve patient adherence and persistence and fight against clinical inertia. This article reviews the results of major randomized controlled trials in people with type2 diabetes that compared iGlarLixi to other therapeutic regimens, representing different intensification strategies, such as basal supported oral therapy, oral antidiabetic drugs, and a combination of the latter with glucagon-like peptide1 receptor agonists. Moreover, as a supplement to randomized trials, data from real-world evidence have also been included.

Tenecteplase: A Review of Its Pharmacology and Uses.

Tenecteplase: A Review of Its Pharmacology and Uses.

Guideline-Directed Medical Therapy for the Treatment of Heart Failure with Reduced Ejection Fraction.

Guideline-directed medical therapy (GDMT) is the cornerstone of pharmacological therapy for patients with heart failure with reduced ejection fraction (HFrEF) and consists of the four main drug classes: renin-angiotensin system inhibitors, evidence-based β-blockers, mineralocorticoid inhibitors and sodium glucose cotransporter 2 inhibitors. The recommendation for use of GDMT is based on the results of multiple major randomized controlled trials demonstrating improved clinical outcomes in patients with HFrEF who are maintained on this therapy. The effect is most beneficial when medications from the four main drug classes are used in conjunction. Despite this, there is an underutilization of GDMT, partially due to lack of awareness of how to safely and effectively initiate and titrate these medications. In this review article, we describe the different drug classes included in GDMT and offer an approach to initiation and effective titration in both the inpatient as well as outpatient setting.

The Effect of Oral Magnesium Supplement on Pre-eclampsia and Perinatal Outcomes in Pregnancy: A Meta-Analysis of Randomized Controlled Trials

Background: Magnesium is one of the most important nutritional factors that have a beneficial effect on pregnant women. Many studies evaluated the role of oral magnesium supplements as a non-pharmacological intervention for mother and neonatal protection in terms of these outcomes. There is a conflict between several clinical trials about the efficacy of oral magnesium supplements during pregnancy. Therefore, in this review, we represent class 1 evidence and address an unmet clinical need on the efficacy of different types of oral magnesium in pre-eclampsia, and prenatal outcomes in pregnant women.&#x0D; Method: During the preparation of this meta-analysis, we followed the PRISMA statement guidelines. A literature search of the Web of Sciences, Cochrane Central Register of Controlled Trials, and PubMed were conducted from inception until September 2022. We included randomized controlled trials (RCTs) comparing oral magnesium whether citrate, oxide, or aspartate hydrochloride with a placebo. The records of quality studies were screened and extracted. Additionally, the pre-eclampsia, preterm birth, and neonatal intensive care unit (NICU) admissions data were pooled as odds ratio (OR) in a fixed-effect model using Review Manager (v.3). Subgroup analysis was performed to investigate the efficacy of each type of oral magnesium on the outcomes.&#x0D; Results: Five RCTs were included in this meta-analysis with a total of 2370 patients. The overall effect did not favor either of the two groups in terms of pre-eclampsia (OR= 0.99, 95% CI, [0.72, 1.37], p = 0.9), preterm birth (OR= 0.87, 95% CI, [0.62, 1.22], p = 0.4), and NICU admissions (OR= 1.37, 95% CI, [0.84, 2.22], p = 0.2). Based on the subgroup analysis findings, the use of oral magnesium supplements whether citrate, oxide, or aspartate hydrochloride in this population did not significantly increase or decrease the incidence of pre-eclampsia, preterm birth, and NICU admissions when compared with the control group.&#x0D; Conclusion: Ultimately, oral magnesium supplementation whether citrate, oxide, or aspartate hydrochloride may not have a beneficial effect on maternal and fetal outcomes during pregnancy. Therefore, the current evidence is insufficient to confirm the efficacy of oral magnesium for care practice among pregnant women. Despite that, these results need to be affirmed by major RCTs using magnesium supplements which have related to neonatal and maternal outcomes.

Head CT deep learning model is highly accurate for early infarct estimation

Non-contrast head CT (NCCT) is extremely insensitive for early (< 3–6 h) acute infarct identification. We developed a deep learning model that detects and delineates suspected early acute infarcts on NCCT, using diffusion MRI as ground truth (3566 NCCT/MRI training patient pairs). The model substantially outperformed 3 expert neuroradiologists on a test set of 150 CT scans of patients who were potential candidates for thrombectomy (60 stroke-negative, 90 stroke-positive middle cerebral artery territory only infarcts), with sensitivity 96% (specificity 72%) for the model versus 61–66% (specificity 90–92%) for the experts; model infarct volume estimates also strongly correlated with those of diffusion MRI (r2 > 0.98). When this 150 CT test set was expanded to include a total of 364 CT scans with a more heterogeneous distribution of infarct locations (94 stroke-negative, 270 stroke-positive mixed territory infarcts), model sensitivity was 97%, specificity 99%, for detection of infarcts larger than the 70 mL volume threshold used for patient selection in several major randomized controlled trials of thrombectomy treatment.

Heart failure: an update from the last years and a look at the near future.

In the last years, major progress occurred in heart failure (HF) management. Quadruple therapy is now mandatory for all the patients with HF with reduced ejection fraction. Whilst verciguat is becoming available across several countries, omecamtiv mecarbil is waiting to be released for clinical use. Concurrent use of potassium-lowering agents may counteract hyperkalaemia and facilitate renin-angiotensin-aldosterone system inhibitor implementations. The results of the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trial were confirmed by the Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER) trial, and we now have, for the first time, evidence for treatment of also patients with HF with preserved ejection fraction. In a pre-specified meta-analysis of major randomized controlled trials, sodium-glucose co-transporter-2 inhibitors reduced all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in the patients with HF regardless of left ventricular ejection fraction. Other steps forward have occurred in the treatment of decompensated HF. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload (ADVOR) trial showed that the addition of intravenous acetazolamide to loop diuretics leads to greater decongestion vs. placebo. The addition of hydrochlorothiazide to loop diuretics was evaluated in the CLOROTIC trial. Torasemide did not change outcomes, compared with furosemide, in TRANSFORM-HF. Ferric derisomaltose had an effect on the primary outcome of CV mortality or HF rehospitalizations in IRONMAN (rate ratio 0.82; 95% confidence interval 0.66-1.02; P=0.070). Further options for the treatment of HF, including device therapies, cardiac contractility modulation, and percutaneous treatment of valvulopathies, are summarized in this article.

Controversies in the management of proximal deep vein thrombosis.

Controversies in the management of proximal deep vein thrombosis.

Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: results of 10 years of use

The article presents a review of the basic data on the efficacy and safety of the drug tofacitinib, the place of the drug in the treatment of rheumatoid arthritis (RA) patients according to current international and Russian recommendations. Data on the mechanism of action of Janus kinase inhibitors, the spectrum of cytokines inhibited by tofacitinib is presented. The results of major randomised controlled trials demonstrating high clinical efficacy in patients who have not responded to methotrexate (MT) and other synthetic classical anti-rheumatic drugs (SCARDs), genetically engineered biologic drugs, are presented, with equal efficacy of tofacitinib when given as monotherapy or in combination with MT or other SCARDs, with adalimumab. The safety of tofacitinib with long-term treatment (up to 9.5 years) is analysed. The cardiovascular tolerability of tofacitinib is presented separately, considering the proposals discussed at the last EULAR 2022 Congress. The low incidence of serious cardiovascular adverse events, including venous thrombosis and thromboembolism over the long-term follow-up period, and the risk of these adverse events, which was no higher than on the selective Janus kinase inhibitor baricitinib, are presented. Changes in laboratory parameters (haemoglobin, neutrophil count, aminotransferase concentration) during tofacitinib administration are described. Domestic data on the use of tofacitinib in the treatment of RA patients is demonstrated. An association was shown between early clinical response to tofacitinib (5 mg twice daily) and a reduction in RA activity after 3 and 6 months in RA patients. Tofacitinib in real clinical practice showed early development of effect (by week 12) in the group of patients who did not respond to MT and in 60% of cases to genetically engineered biologic drugs, with respect to indicators of inflammatory activity of RA and functional status of patients. Domestic authors have noted the high safety of tofacitinib. A domestic generic version of the original drug tofacitinib has been reported to be registered for the same indications: RA, psoriatic arthritis, plaque psoriasis, ulcerative colitis.

Managing Heart Failure with Preserved Ejection Fraction; A Short Review of Latest Evidences

Heart failure with preserved ejection fraction (HFpEF) is a clinical dilemma and various clinical trials so far have failed to give a concrete evidence of reducing mortality and major adverse cardiac events (MACE) in this condition. A detailed analysis of the existing evidences and a future plan for a concrete trial design with long duration of follow up is needed to address the dilemma of Heart failure with preserved ejection fraction.&#x0D; The objective of this short review was to review the latest and major randomized controlled trials and study the primary outcomes. The public database of PubMed, Google Scholar and Cochrane were extensively searched for all randomized controlled trials using keywords of Heart failure with preserved ejection fraction, major adverse cardiac events, Hospitalizations; and studies were included in the review if data were reported for patients with ejection fraction &gt; 40%, did not include congenital heart disease, and demonstrated evidence of diastolic failure on echocardiogram (ECHO), and evaluated hospitalizations, major adverse cardiac events and cardiovascular mortality.&#x0D; Despite the major trials reporting improved primary composite endpoints with newer drugs the results have to be interpreted cautiously since the primary outcome were mostly driven by heart failure hospitalizations and not mortality reduction.

Current recommendations for revascularization of non-infarct-related artery in patients presenting with ST-segment elevation myocardial infarction and multivessel disease.

ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality worldwide. Immediate reperfusion therapy of the infarct-related artery (IRA) is the mainstay of treatment, either via primary percutaneous coronary intervention (PPCI) or thrombolytic therapy when PPCI is not feasible. Several studies have reported the incidence of multivessel disease (MVD) to be about 50% of total STEMI cases. This means that after successful PPCI of the IRA, residual lesion(s) of the non-IRA may persist. Unlike the atherosclerotic plaque of stable coronary artery disease, the residual obstructive lesion of the non-IRA contains a significantly higher prevalence of vulnerable plaques. Since these lesions are a strong predictor of acute coronary syndrome, if left untreated they are a possible cause of future adverse cardiovascular events. Percutaneous coronary intervention (PCI) of the obstructive lesion of the non-IRA to achieve complete revascularization (CR) is therefore preferable. Several major randomized controlled trials (RCTs) and meta-analyses demonstrated the clinical benefits of the CR strategy in the setting of STEMI with MVD, not only for enhancing survival but also for reducing unplanned revascularization. The CR strategy is now supported by recently published clinical practice guidelines. Nevertheless, the benefit of revascularization must be weighed against the risks from additional procedures.

Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status.

Roy PP, Mahtab MA, Rahim MA, et al. Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S46-S50.

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.

Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood pressure. We conducted a one-stage individual participant-level data meta-analysis of major randomised controlled trials using the Blood Pressure Lowering Treatment Trialists' Collaboration dataset. Trials with information on type 2 diabetes status at baseline were eligible if they compared blood pressure-lowering medications versus placebo or other classes of blood pressure-lowering medications, or an intensive versus a standard blood pressure-lowering strategy, and reported at least 1000 persons-years of follow-up in each group. Trials exclusively on participants with heart failure or with short-term therapies and acute myocardial infarction or other acute settings were excluded. We expressed treatment effect per 5 mm Hg reduction in systolic blood pressure on the risk of developing a major cardiovascular event as the primary outcome, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal ischaemic heart disease, or heart failure causing death or requiring hospitalisation. Cox proportional hazard models, stratified by trial, were used to estimate hazard ratios (HRs) separately by type 2 diabetes status at baseline, with further stratification by baseline categories of systolic blood pressure (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg). To estimate absolute risk reductions, we used a Poisson regression model over the follow-up duration. The effect of each of the five major blood pressure-lowering drug classes, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β blockers, calcium channel blockers, and thiazide diuretics, was estimated using a network meta-analysis framework. This study is registered with PROSPERO, CRD42018099283. We included data from 51 randomised clinical trials published between 1981 and 2014 involving 358 533 participants (58% men), among whom 103 325 (29%) had known type 2 diabetes at baseline. The baseline mean systolic/diastolic blood pressure of those with and without type 2 diabetes was 149/84 mm Hg (SD 19/11) and 153/88 mm Hg (SD 21/12), respectively. Over 4·2 years median follow-up (IQR 3·0-5·0), a 5 mm Hg reduction in systolic blood pressure decreased the risk of major cardiovascular events in both groups, but with a weaker relative treatment effect in participants with type 2 diabetes (HR 0·94 [95% CI 0·91-0·98]) compared with those without type 2 diabetes (0·89 [0·87-0·92]; pinteraction=0·0013). However, absolute risk reductions did not differ substantially between people with and without type 2 diabetes because of the higher absolute cardiovascular risk among participants with type 2 diabetes. We found no reliable evidence for heterogeneity of treatment effects by baseline systolic blood pressure in either group. In keeping with the primary findings, analysis using stratified network meta-analysis showed no evidence that relative treatment effects differed substantially between participants with type 2 diabetes and those without for any of the drug classes investigated. Although the relative beneficial effects of blood pressure reduction on major cardiovascular events were weaker in participants with type 2 diabetes than in those without, absolute effects were similar. The difference in relative risk reduction was not related to the baseline blood pressure or allocation to different drug classes. Therefore, the adoption of differential blood pressure thresholds, intensities of blood pressure lowering, or drug classes used in people with and without type 2 diabetes is not warranted. British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.