ABSTRACT Background Mineralocorticoid receptor antagonists (MRAs) reduce systolic blood pressure (SBP) and increase serum potassium concentration ([K+]). This indirect comparison investigated any differences in SBP-lowering and hyperkalemia risk between finerenone, a nonsteroidal MRA, and the steroidal MRA spironolactone ± a potassium binder. Methods In FIDELITY (a pooled analysis of FIDELIO-DKD and FIGARO-DKD), a subgroup of patients with treatment-resistant hypertension (TRH) and chronic kidney disease meeting eligibility criteria of the AMBER trial were identified (FIDELITY-TRH). The main outcomes were mean change in SBP, incidence of serum [K+] ≥5.5 mmol/L and hyperkalemia-associated treatment discontinuation. Results at ∼17 weeks were compared with 12 weeks from AMBER. Results In 624 FIDELITY-TRH patients and 295 AMBER patients, the least squares mean change in SBP (mmHg) from baseline was −7.1 for finerenone and −1.3 for placebo {between-group difference −5.74 [95% confidence interval (CI) −7.99 to −3.49], P < .0001} versus −11.7 for spironolactone + patiromer and −10.8 for spironolactone + placebo [between-group difference −1.0 (95% CI −4.4–2.4), P = .58]. The incidence of serum [K+] ≥5.5 mmol/L was 12% for finerenone and 3% for placebo versus 35% with spironolactone + patiromer and 64% with spironolactone + placebo. Treatment discontinuation due to hyperkalemia was 0.3% for finerenone and 0% for placebo versus 7% for spironolactone + patiromer and 23% for spironolactone + placebo. Conclusions In patients with TRH and chronic kidney disease compared with spironolactone with or without patiromer, finerenone was associated with a lower SBP reduction and lower risk of hyperkalemia and treatment discontinuation. Trial Registration: AMBER (NCT03071263), FIDELIO-DKD (NCT02540993), FIGARO-DKD (NCT02545049)

In Fig. 2 of the article cited above, due to a typographical error, the hazard ratio (HR) of the key secondary composite kidney outcome in the insulin at baseline subgroup was incorrectly reported as 0.74 (95% CI 0.59-0.94) instead of the correct HR of 0.77 (95% CI 0.62-0.94). In addition, the HRs of the secondary composite cardiovascular outcome were incorrectly reported as 0.88 (95% CI 0.71-1.09) for no insulin at baseline and 0.83 (95% CI 0.69-1.01) for insulin at baseline (P for interaction 0.70). The correct HRs for the secondary composite cardiovascular outcome are 0.95 (95% CI 0.74-1.23) for no insulin at baseline and 0.82 (95% CI 0.69-0.97) for insulin at baseline (P for interaction 0.33). The authors apologize for the error. The online version of the article (https://doi.org/10.2337/dc21-1944) has been updated to correct the error.

Objective: Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in FIDELIO-DKD. We explored whether baseline HbA1c and insulin treatment influenced outcomes.Research design and methods: Patients with T2D, urine albumin-to-creatinine ratio (UACR) 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) 25–<75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomized to finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% or ≥7.5%.Results: Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c and insulin use (Pinteraction 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c and insulin use (Pinteraction 0.70 and 0.33, respectively). Although baseline HbA1c did not affect kidney event risk, cardiovascular risk increased with higher HbA1c. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment due to hyperkalemia.Conclusion: Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D and risks appear consistent irrespective of HbA1c levels or insulin use.

Introduction: Patients with CKD and T2D are at high risk of morbidity and mortality despite the use of guideline-directed therapies. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, reduced the risk of adverse kidney and CV outcomes in patients with CKD and T2D; here we report outcomes by baseline A1C. Methods: FIDELIO-DKD (NCT02540993) randomized 5734 patients from 48 countries to receive oral finerenone or placebo. Eligible patients had T2D, with a UACR of ≥30-≤5000 mg/g, eGFR ≥25‍-‍<75 mL/min/1.73 m2 and received optimized RAS blockade. Patients with A1C >12% at screening were excluded. The primary outcome was a composite of kidney failure, sustained ≥40% decrease in eGFR from baseline, or renal death. The key secondary outcome was a composite of CV death, non-fatal MI, non-fatal stroke, or hospitalization for HF. Results: In the 5674 patients analyzed, the mean baseline A1C was 7.7% and mean diabetes duration was 16.6 years; finerenone did not affect A1C during the trial. Overall, 2948 patients had A1C ≤7.5% and 2715 patients had A1C >7.5% at baseline. Patients with higher A1C levels were more likely to use insulin and had a longer duration of diabetes. After a median follow-up of 2.6 years, the primary outcome occurred in fewer patients treated with finerenone compared with placebo, this was observed in both the A1C ≤7.5% and >7.5% groups (18.7% vs. 21.5% patients with A1C of ≤7.5% [HR 0.86; 95% CI 0.73-1.01]; 16.9% vs. 20.7% patients with A1C >7.5% [HR 0.79; 95% CI 0.66-0.94]; P-interaction 0.47). Finerenone also reduced the incidence of the key secondary CV outcome compared with placebo regardless of baseline A1C (HR 0.88; 95% CI 0.71-1.07 for A1C ≤7.5% and HR 0.83; 95% CI 0.69-1.01 for A1C >7.5%; P-interaction 0.73). Reduction in UACR was consistent across subgroups. Overall, hyperkalemia events were independent of A1C level. Conclusion: In patients with CKD and T2D, treatment with finerenone reduced the risk for developing adverse kidney and CV outcomes independent of baseline A1C. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. M. Brinker: Employee; Self; Bayer AG, Stock/Shareholder; Self; Bayer AG. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck & Co., Inc., Vascular Dynamics Inc. E. Burgess: Advisory Panel; Self; Bayer Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. P. Gillard: None. A. Joseph: Employee; Self; Bayer AG. Funding Bayer AG

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

PURPOSE:Several options are available for the treatment of hypertension; however, many treated patients are still not below blood pressure (BP) target. Eplerenone, a selective mineralocorticoid receptor antagonist, is an approved treatment option for the management of patients with hypertension in a number of countries. This patient-level pooled analysis was conducted to document the efficacy and safety/tolerability of eplerenone at the dosages approved for use in hypertension in comparison to placebo or other approved antihypertensive agents. METHODS:Seventeen Phase III studies conducted in patients with mild-to-moderate hypertension in the Eplerenone Hypertension Clinical Program were reviewed; eleven met the selection criteria. The primary endpoint was change from baseline in seated diastolic BP and seated systolic BP measured at the end of the study. RESULTS:A total of 2,698 patients were included in this per-protocol analysis. In patients treated for at least 6 weeks with a stable dose of eplerenone, doses of 50 mg daily and 100 mg daily were associated with greater reductions of seated systolic BP and seated diastolic BP compared with placebo (P<0.001) and active-controlled studies (P< 0.033). In the analysis of covariance model testing of the contribution of four factors (age, body mass index [BMI], history of cardiovascular disease, and diabetes) on the BP lowering effects of eplerenone, only BMI and age were associated with small though statistically significant changes in BP (<0.2 mmHg). Eplerenone was well tolerated; headache was the most common adverse event for patients in any group. Severe hyperkalemia (serum potassium level >6.0 mmol/L) occurred in up to 0.4% in the eplerenone groups, 0.4% in the placebo group, and 0.1% in the active-control group. CONCLUSION:This patient-level pooled analysis provides robust evidence that eplerenone, at 50 mg or 100 mg daily, was effective in lowering BP in patients with mild-to-moderate hypertension and was well tolerated.

Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children. This year, the adult and pediatric guidelines are combined in one document. The new 2018 pregnancy-specific hypertension guidelines are published separately. For 2018, 5 new guidelines are introduced, and 1 existing guideline on the blood pressure thresholds and targets in the setting of thrombolysis for acute ischemic stroke is revised. The use of validated wrist devices for the estimation of blood pressure in individuals with large arm circumference is now included. Guidance is provided for the follow-up measurements of blood pressure, with the use of standardized methods and electronic (oscillometric) upper arm devices in individuals with hypertension, and either ambulatory blood pressure monitoring or home blood pressure monitoring in individuals with white coat effect. We specify that all individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure. Finally, an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in individuals with heart failure (with ejection fraction < 40%) who are symptomatic despite appropriate doses of guidelinedirected heart failure therapies. The specific evidence and rationale underlying each of these guidelines are discussed.

After the 2016 guidelines for blood pressure measurement, diagnosis, and investigation of pediatric hypertension, we now present evidence-based guidelines for the prevention and treatment of hypertension in children. These guidelines were developed by Hypertension Canada's Guideline Committee pediatric subgroup after thorough evaluation of the available literature. Included are 10 guidelines specifically addressing health behaviour management, indications for drug therapy in children with hypertension, choice of therapy for children with primary hypertension, and goals of therapy for children with hypertension. Although the pediatric literature is inherently limited by small numbers of participants, fewer trials, and a prolonged latency to the development of vascular outcomes, this report reflects the current and highest level of evidence and provides guidance for primary care practitioners on the management of pediatric hypertension. Studies of therapeutic lifestyle modifications in children are available to guide current management and more antihypertensive drugs have been studied in children since the Food and Drug Administration Modernization Act. Consistent with Hypertension Canada's guideline policy, diagnostic and therapeutic algorithm tools will be developed and the guidelines will be reviewed annually and updated according to new evidence.

We present the inaugural evidence-based Canadian recommendations for the measurement of blood pressure in children and the diagnosis and evaluation of pediatric hypertension. Rates of pediatric hypertension are increasing concomitant with increased rates of childhood obesity. With this, there is growing awareness of the need to measure blood pressure in children. Consequently, the present recommendations have been developed to address an important gap and improve the clinical care of children. For 2016, a total of 15 recommendations are presented. These are categorized in a fashion similar to that of the existing adult recommendations. Specifically, we present recommendations on (1) accurate measurement of blood pressure in children, (2) criteria for diagnosis of hypertension in children, (3) assessment of overall cardiovascular risk in hypertensive children, (4) routine laboratory tests for the investigation of children with hypertension, (5) ambulatory blood pressure measurement in children, and (6) the role of echocardiography. We discuss the rationale for the recommendations and present additional supporting material for the clinician, including tables with standardized techniques for blood pressure measurement and determination of normative blood pressure values for children. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will update the recommendations annually and develop future evidence-based recommendations to guide prevention and treatment of pediatric hypertension.

Hypertension in renal transplant recipients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular morbidity and mortality and shortened allograft survival are important consequences of inadequate control of hypertension. In this review, we examine the epidemiology, pathophysiology, and management considerations of post-transplant hypertension. Donor and recipient factors, acute and chronic allograft injury, and immunosuppressive medications may each explain some of the pathophysiology of post-transplant hypertension. As observed in other patient cohorts, renal artery stenosis and adrenal causes of hypertension may be important contributing factors. Notably, BP treatment goals for renal transplant recipients remain an enigma because there are no adequate randomized controlled trials to support a benefit from targeting lower BP levels on graft and patient survival. The potential for drug-drug interactions and altered pharmacokinetics and pharmacodynamics of the different antihypertensive medications need to be carefully considered. To date, no specific antihypertensive medications have been shown to be more effective than others at improving either patient or graft survival. Identifying the underlying pathophysiology and subsequent individualization of treatment goals are important for improving long-term patient and graft outcomes in these patients.

Herein, updated evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in Canadian adults are detailed. For 2014, 3 existing recommendations were modified and 2 new recommendations were added. The following recommendations were modified: (1) the recommended sodium intake threshold was changed from ≤ 1500 mg (3.75 g of salt) to approximately 2000 mg (5 g of salt) per day; (2) a pharmacotherapy treatment initiation systolic blood pressure threshold of ≥ 160 mm Hg was added in very elderly (age ≥ 80 years) patients who do not have diabetes or target organ damage (systolic blood pressure target in this population remains at < 150 mm Hg); and (3) the target population recommended to receive low-dose acetylsalicylic acid therapy for primary prevention was narrowed from all patients with controlled hypertension to only those ≥ 50 years of age. The 2 new recommendations are: (1) advice to be cautious when lowering systolic blood pressure to target levels in patients with established coronary artery disease if diastolic blood pressure is ≤ 60 mm Hg because of concerns that myocardial ischemia might be exacerbated; and (2) the addition of glycated hemoglobin (A1c) in the diagnostic work-up of patients with newly diagnosed hypertension. The rationale for these recommendation changes is discussed. In addition, emerging data on blood pressure targets in stroke patients are discussed; these data did not lead to recommendation changes at this time. The Canadian Hypertension Education Program recommendations will continue to be updated annually.

Does sodium restriction reduce mortality from cardiovascular disease (CVD)? Meta-analyses suggest that moderate sodium reduction (from 3900 mg to 3000 mg a day) can reduce CVD events, but the effect on mortality is unclear. More evidence with clinical outcomes is required to better define optimal

The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment. This report provides the updated evidence-based recommendations for 2015. This year, 4 new recommendations were added and 2 existing recommendations were modified. A revised algorithm for the diagnosis of hypertension is presented. Two major changes are proposed: (1) measurement using validated electronic (oscillometric) upper arm devices is preferred over auscultation for accurate office blood pressure measurement; (2) if the visit 1 mean blood pressure is increased but < 180/110 mm Hg, out-of-office blood pressure measurements using ambulatory blood pressure monitoring (preferably) or home blood pressure monitoring should be performed before visit 2 to rule out white coat hypertension, for which pharmacologic treatment is not recommended. A standardized ambulatory blood pressure monitoring protocol and an update on automated office blood pressure are also presented. Several other recommendations on accurate measurement of blood pressure and criteria for diagnosis of hypertension have been reorganized. Two other new recommendations refer to smoking cessation: (1) tobacco use status should be updated regularly and advice to quit smoking should be provided; and (2) advice in combination with pharmacotherapy for smoking cessation should be offered to all smokers. The following recommendations were modified: (1) renal artery stenosis should be primarily managed medically; and (2) renal artery angioplasty and stenting could be considered for patients with renal artery stenosis and complicated, uncontrolled hypertension. The rationale for these recommendation changes is discussed.

Background and Objectives There is little information on the effects of trandolapril on renal function when used in Canadian general practice. We evaluated the use and blood pressure (BP) lowering effectiveness of trandolapril-based therapies in Canadian conditions of actual care and attempted to capture assessments of urinary albumin concentration (UAC) and estimated glomerular filtration rate (eGFR) in clinical practice. Methods This was a prospective, non-interventional, observational study in adults with uncontrolled hypertension, with or without co-morbidities, either treatment-naïve or uncontrolled on existing antihypertensive medications. Hypertension was not defined per protocol. Trandolapril doses (0.5, 1, 2, 4 mg) and subjects’ continued medical care were all at the discretion of the treating physician. Data were gathered after 3, 6 and 12 months. Results 7,993 patients entered the study and 4,983 patients attended the Month 12 visit. Most patients (91.7 %) received trandolapril as a new prescription. At 12 months, 72.9 % of patients without diabetes and 34.4 % with diabetes were controlled (targets <140/90 and 130/80 mmHg, respectively) and 79.2 % of patients with diabetes had BP below 140/90 mmHg. Evaluable eGFR data were available for 25.1, 21.2 and 21.7 % of patients at Months 3, 6 and 12, respectively, and UAC data for 9.6, 8.2 and 9.0 % of patients at the same time points. Treatment was well tolerated. Dropout rates were 37.7 % after 12 months. Conclusion Effective, sustained and well-tolerated double-digit BP reduction is achievable with a trandolapril-based treatment regimen for all patient groups. It appears that for diabetic patients blood pressure control as per Canadian Hypertension Education Program recommendations is yet challenging. The results also illuminate the persistent gap between treatment guidelines and actual care.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2012. The new recommendations are: (1) use of home blood pressure monitoring to confirm a diagnosis of white coat syndrome; (2) mineralocorticoid receptor antagonists may be used in selected patients with hypertension and systolic heart failure; (3) a history of atrial fibrillation in patients with hypertension should not be a factor in deciding to prescribe an angiotensin-receptor blocker for the treatment of hypertension; and (4) the blood pressure target for patients with nondiabetic chronic kidney disease has now been changed to < 140/90 mm Hg from < 130/80 mm Hg. We also reviewed the recent evidence on blood pressure targets for patients with hypertension and diabetes and continue to recommend a blood pressure target of less than 130/80 mm Hg.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2011. The major guideline changes this year are: (1) a recommendation was made for using comparative risk analogies when communicating a patient's cardiovascular risk; (2) diagnostic testing issues for renal artery stenosis were discussed; (3) recommendations were added for the management of hypertension during the acute phase of stroke; (4) people with hypertension and diabetes are now considered high risk for cardiovascular events if they have elevated urinary albumin excretion, overt kidney disease, cardiovascular disease, or the presence of other cardiovascular risk factors; (5) the combination of an angiotensin-converting enzyme (ACE) inhibitor and a dihydropyridine calcium channel blocker (CCB) is preferred over the combination of an ACE inhibitor and a thiazide diuretic in persons with diabetes and hypertension; and (6) a recommendation was made to coordinate with pharmacists to improve antihypertensive medication adherence. We also discussed the recent analyses that examined the association between angiotensin II receptor blockers (ARBs) and cancer.