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Antihypertensive treatment is equally beneficial for reducing cardiovascular risk in both men and women. Despite this, the drug treatment, prevalence and control of hypertension differ between men and women. Men and women respond differently, particularly with respect to the risk of adverse events, to many antihypertensive drugs. Certain antihypertensive drugs may also be especially beneficial in the setting of certain comorbidities – of both cardiovascular and extracardiac nature – which also differ between men and women. Furthermore, hypertension in pregnancy can pose a considerable therapeutic challenge for women and their physicians in primary care. In addition, data from population-based studies and from real-world data are inconsistent regarding whether men or women attain hypertension-related goals to a higher degree. In population-based studies, women with hypertension have higher rates of treatment and controlled blood pressure than men, whereas real-world, primary-care data instead show better blood pressure control in men. Men and women are also treated with different antihypertensive drugs: women use more thiazide diuretics and men use more angiotensin-enzyme inhibitors and calcium-channel blockers. This narrative review explores these sex-related differences with guidance from current literature. It also features original data from a large, Swedish primary-care register, which showed that blood pressure control was better in women than men until they reached their late sixties, after which the situation was reversed. This age-related decrease in blood pressure control in women was not, however, accompanied by a proportional increase in use of antihypertensive drugs and female sex was a significant predictor of less intensive antihypertensive treatment.

Objective To assess the relation between socioeconomic status and achievement of target blood pressure in hypertension. Design Retrospective longitudinal cohort study between 2001 and 2014. Setting Primary health care in Skaraborg, Sweden. Subjects 48,254 patients all older than 30 years, and 53.3% women, with diagnosed hypertension. Main outcome measures Proportion of patients who achieved a blood pressure target

Background: European treatment guidelines recommend prasugrel over ticagrelor for treating patients with non–ST-elevation acute coronary syndrome (ACS), prompting several Swedish administrative regions to transition from ticagrelor to prasugrel as the preferred treatment for patients with ACS. We aim to systematically evaluate this transition to determine the relative efficacy of prasugrel versus ticagrelor in a real-world cohort of patients with ACS. Study design and objectives: The SWITCH SWEDEHEART trial is a prospective, multicenter, open-label, cross-sectional, stepped-wedge cluster-randomized clinical trial, in which administrative regions in Sweden will constitute the clusters. At the start of the study, all clusters will use ticagrelor as the P2Y12 inhibitor drug of choice for ACS. The order in which the clusters will implement the transition from ticagrelor to prasugrel will be randomly assigned. Every 9 months, 1 cluster will switch from ticagrelor to prasugrel as the P2Y12 inhibitor of choice for patients with ACS. The primary endpoint is the composite 1-year rate of the death, stroke, or myocardial infarction. Conclusions: The SWITCH SWEDEHEART study will provide an extensive randomized comparison between ticagrelor and prasugrel. Novel therapies are frequently costly and supported by evidence from few or small studies, and systematic evaluation after the introduction is rare. This study will establish an important standard for introducing and evaluating the effects of health care changes within our societies.

Objective To assess the risk of haemorrhagic stroke at different baseline SBP levels in a primary care population with hypertension, atrial fibrillation and newly initiated oral anticoagulants (OACs). Methods We identified 3972 patients with hypertension, atrial fibrillation and newly initiated OAC in The Swedish Primary Care Cardiovascular Database of Skaraborg. Patients were followed from 1 January 2006 until a first event of haemorrhagic stroke, death, cessation of OAC or 31 December 2016. We analysed the association between continuous SBP and haemorrhagic stroke with a multivariable Cox regression model and plotted the hazard ratio as a function of SBP with a restricted cubic spline with 130 mmHg as reference. Results There were 40 cases of haemorrhagic stroke during follow-up. Baseline SBP in the 145-180 mmHg range was associated with a more than doubled risk of haemorrhagic stroke, compared with a SBP of 130 mmHg. Conclusion In this cohort of primary care patients with hypertension and atrial fibrillation, we found that baseline SBP in the 145-180 mmHg range, prior to initiation of OAC, was associated with a more than doubled risk of haemorrhagic stroke, as compared with an SBP of 130 mmHg. This suggests that lowering SBP to below 145 mmHg, prior to initiation of OAC, may decrease the risk of haemorrhagic stroke in patients with hypertension and atrial fibrillation.

OBJECTIVE The sodium–glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. This report explores the effect of dapagliflozin on incident type 2 diabetes (T2D) in the cohort without diabetes enrolled in the trial. RESEARCH DESIGN AND METHODS The subgroup of 2,605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and an HbA1c of RESULTS At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, with a placebo-adjusted change in the dapagliflozin group of −0.04%. Over a median follow-up of 18 months, diabetes developed in 93 of 1,307 patients (7.1%) in the placebo group and 64 of 1,298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (hazard ratio 0.68, 95% CI 0.50–0.94; P = 0.019). More than 95% of the participants who developed T2D had prediabetes at baseline (HbA1c 5.7–6.4%). Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not. CONCLUSIONS In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure.

Aims We investigated the 2 year rate of ischaemic stroke/transient ischaemic attack (IS) in patients with heart failure (HF) who were in sinus rhythm (HF-SR) and aimed to develop a score for stratifying risk of IS in this population. Methods and results A total of 15 425 patients (mean age 71.5 years, 39% women) with HF-SR enrolled in the Swedish Heart Failure Register were included; 28 815 age-matched and sex-matched controls, without a registered diagnosis of HF, were selected from the Swedish Population Register. The 2 year rate of IS was 3.0% in patients and 1.4% in controls. In the patient group, a risk score including age (1p for 65-74 years; 2p for 75-84 years; 3p for >= 85 years), previous IS (2p), ischaemic heart disease, diabetes, hypertension, kidney dysfunction, and New York Heart Association III/IV class (1p each) was generated. Over a mean follow-up of 20.1 (SD 7.5) months, the cumulative incidences (per 1000 person-years) of IS in patients with score 0 to >= 7 were 2.2, 5.3, 8.9, 13.2, 15.7, 20.4, 26.4, and 33.0, with hazard ratios for score 1 to >= 7 (with 0 as reference): 2.4, 4.1, 6.1, 7.2, 9.4, 12.2, and 15.3. The risk score performed modestly (area under the curve 63.7%; P = 0.4711 for lack of fit with a logistic model; P = 0.7062 with Poisson, scaled by deviance). Conclusions In terms of absolute risk, only 27.6% of patients had an annual IS incidence of Funding Agencies|Swedish government [ALFGBG-717211]; County Councils Concerning Economic Support of Research and Education of Doctors [ALFGBG-717211]; Swedish Heart and Lung Foundation (Hjart-Lungfonden) [2015-0438, 2018-0366]; Swedish Research Council (Vetenskapsradet)Swedish Research Council [2013-05187, 2018-02527]

The cardiovascular risk conferred by concomitant prediabetes in hypertension is unclear. We aimed to examine the impact of prediabetes on incident heart failure (HF) and all-cause mortality, and to describe time in therapeutic blood pressure range (TTR) in a hypertensive real-world primary care population.In this retrospective cohort study, 9628 hypertensive individuals with a fasting plasma glucose (FPG) in 2006-2010 but no diabetes, cardiovascular or renal disease were followed to 2016; median follow-up was 9 years. Prediabetes was defined as FPG 5.6-6.9 mmol/L, and in a secondary analysis as 6.1-6.9 mmol/L. Study outcomes were HF and all-cause mortality. Hazard ratios (HR) were compared for prediabetes with normoglycemia using Cox regression. All blood pressure values from 2001 to the index date (first FPG in 2006-2010) were used to calculate TTR. At baseline, 51.4% had prediabetes. The multivariable-adjusted HR (95% confidence intervals) was 0.86 (0.67-1.09) for HF and 1.06 (0.90-1.26) for all-cause mortality. For FPG defined as 6.1-6.9 mmol/L, the multivariable-adjusted HR were 1.05 (0.80-1.39) and 1.42 (1.19-1.70), respectively. The prediabetic group had a lower TTR (p 0.05).Prediabetes was not independently associated with incident HF in hypertensive patients without diabetes, cardiovascular or renal disease. However, prediabetes was associated with all-cause mortality when defined as FPG 6.1-6.9 mmol/L (but not as 5.6-6.9 mmol/L). TTR was lower in the prediabetic group, suggesting room for improved blood pressure to reduce incident heart failure in prediabetes.

Importance: Sodium glucose cotransporter 2 inhibitors reduce morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Clinicians may find estimates of the projected long-term benefits of sodium glucose cotransporter 2 inhibitors a helpful addition to clinical trial results when communicating the benefits of this class of drug to patients. Objective: To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient’s lifetime. Design, Setting, and Participants: Exploratory analysis was performed of Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), a phase 3 randomized, placebo-controlled clinical trial conducted at 410 sites in 20 countries. Patients with an ejection fraction less than or equal to 40% in New York Heart Association functional classification II to IV and elevated plasma levels of N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Mean (SD) duration of follow-up was 17.6 (5.2) months. Interventions: Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy. Main Outcomes and Measures: The primary composite outcome was time to first hospitalization for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient’s lifetime for the primary outcome and the secondary outcome of death from any cause. Results: A total of 4744 patients (1109 women [23.4%]; 3635 men [76.6%]) were randomized in DAPA-HF, with a mean (SD) age of 66.3 (10.9) years. The extrapolated mean event-free survival for an individual aged 65 years from a primary composite end point event was 6.2 years for placebo and 8.3 years for dapagliflozin, representing an event-free survival time gain of 2.1 years (95% CI, 0.8-3.3 years; P = .002). When considering death from any cause, mean extrapolated life expectancy for an individual aged 65 years was 9.1 years for placebo and 10.8 years for dapagliflozin, with a gain in survival of 1.7 years (95% CI, 0.1-3.3; P = .03) with dapagliflozin. Similar results were seen when extrapolated across the age range studied. In analyses of subgroups of patients in DAPA-HF, consistent benefits were seen with dapagliflozin on both event-free and overall survival. Conclusions and Relevance: These findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival. These findings may be helpful in communicating the benefits of this treatment to patients with HFrEF. Trial registration: ClinicalTrials.gov Identifier: NCT03036124.

Importance Women may respond differently to certain treatments for heart failure (HF) with reduced ejection fraction (HFrEF) than men. Objective To investigate the efficacy and safety of dapagliflozin compared with placebo in men and women with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). Design, Setting, and Participants Prespecified subgroup analysis of a phase 3 randomized clinical trial conducted at 410 sites in 20 countries. Patients with New York Heart Association functional class II through IV with an ejection fraction of 40% or less and elevated N-terminal pro-B-type natriuretic peptide were eligible. Data were analyzed between June 2020 and January 2021. Interventions Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy. Main Outcomes and Measures The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Results A total of 4744 patients were randomized in DAPA-HF, of whom 1109 were women (23.4%). Compared with placebo, dapagliflozin reduced the risk of worsening HF events or cardiovascular death to a similar extent in both men and women (hazard ratios, 0.73 [95% CI, 0.63-0.85] and 0.79 [95% CI, 0.59-1.06], respectively;P for interaction = .67). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement in symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score of ≥5 points; men, 59% vs 50%; women, 57% vs 54%;Pfor interaction = .14) and decreased the proportion with worsening symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score decrease of ≥5 points; men, 25% vs 34%; women, 27% vs 31%;Pfor interaction = .15), irrespective of sex. Results were consistent for the Kansas City Cardiomyopathy Questionnaire clinical summary score and overall summary score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either men or women. Conclusions and Relevance Dapagliflozin reduced the risk of worsening HF, cardiovascular death, and all-cause death and improved symptoms, physical function, and health-related quality of life similarly in men and women with heart failure and reduced ejection fraction. In addition, dapagliflozin was safe and well-tolerated irrespective of sex. Trial Registration ClinicalTrials.gov Identifier:NCT03036124

Aims: In heart failure with reduced ejection fraction (HFrEF), there is an ‘obesity paradox’, where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium–glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). Methods and results: Body mass index was examined using standard categories, i.e. underweight (2); normal weight (18.5–24.9 kg/m2); overweight (25.0–29.9 kg/m2); obesity class I (30.0–34.9 kg/m2); obesity class II (35.0–39.9 kg/m2); and obesity class III (≥40 kg/m2). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal-weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16–1.71), overweight 1.18 (0.97–1.42), obesity class II/III 1.37 (1.10–1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58–0.94), overweight 0.81 (0.65–1.02), obesity class I 0.68 (0.50–0.92), obesity class II/III 0.71 (0.51–1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7–1.1) kg (P < 0.001). Conclusion: We confirmed an ‘obesity survival paradox’ in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. Clinical Trial Registration: ClinicalTrials.gov NCT03036124.

Aims Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). Methods and results Key inclusion criteria were: New York Heart Association Class II−IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95 mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP, Graphical Abstract

In DAPA-HF, the SGLT2 inhibitor (i) dapagliflozin (dapa) reduced worsening heart failure (HF) and cardiovascular death in 4744 patients (pts) with HF and reduced ejection fraction (HFrEF.) Only 45% had type 2 diabetes (T2D) at baseline. We evaluated whether dapa reduced the incidence of diabetes in the 55% of pts without T2D. Pts were randomized to dapa 10 mg or placebo and followed for a median of 18.2 months. New-onset T2D was defined as A1c ≥6.5% measured at 2 consecutive study visits post-randomization or investigator-reported new T2D (with the initiation of a glucose-lowering agent.) The effect of dapa on incident T2D was assessed using a Cox proportional hazards model and confirmed with a Fine and Gray competing risk model to account for mortality. Of the 2605 non-T2D pts at baseline, 157 developed T2D on trial, 150 (95.5%) of whom had prediabetes (A1c 5.7-6.4%) (136 [86.6%] using the more restrictive 6.0-6.4% criterion.) Those with incident T2D had a higher mean baseline A1c (6.2 ±0.3 vs. 5.7 ±0.4%; p Disclosure S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck & Co., Inc., vTv Therapeutics. K. Docherty: Speaker’s Bureau; Self; Eli Lilly and Company. Other Relationship; Self; AstraZeneca. L. Kober: Speaker’s Bureau; Self; AstraZeneca, Novartis AG. Other Relationship; Self; AstraZeneca. M.N. Kosiborod: Consultant; Self; Amarin Corporation, Amgen, Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi US, Vifor Pharma Group. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. F. Martinez: Board Member; Self; AstraZeneca, Novartis Pharmaceuticals Corporation. P. Ponikowski: None. M.S. Sabatine: Consultant; Self; Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor Pharmaceuticals, Dyrnamix Inc., Esperion Therapeutics, Inc., IFM Therapeutics, Intarcia Therapeutics, Ionis Pharmaceuticals, Inc., Medicines Company, MedImmune, Merck & Co., Inc. Research Support; Self; Amgen, AstraZeneca, Bayer U.S., Daiichi Sankyo, Eisai Inc., Intarcia Therapeutics, Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis AG, Pfizer Inc., Quark Pharmaceuticals. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. J. Belohlavek: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH. M. Böhm: Speaker’s Bureau; Self; Abbott, Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Medtronic, Novartis Pharmaceuticals Corporation, Servier, Vifor Pharma Group. C. Chiang: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Merck Sharp & Dohme Corp., Novartis AG, Pfizer Inc., Sanofi. R.A. de Boer: Speaker’s Bureau; Self; Abbott, AstraZeneca, Novartis AG, Roche Diagnostics France. M. Diez: Other Relationship; Self; AstraZeneca. A. Dukat: None. C.E.A. Ljungman: Advisory Panel; Self; AstraZeneca, Novartis AG, Pfizer Foundation. Stock/Shareholder; Self; AstraZeneca. Other Relationship; Self; AstraZeneca, Novartis AG. S. Verma: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Other Relationship; Self; AstraZeneca, AstraZeneca, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Eli Lilly and Company, EOCI Pharmacomm, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Canada Inc., Novo Nordisk A/S, Novo Nordisk A/S, Sanofi, Sanofi, Sun Pharmaceuticals, Toronto Knowledge Translation Working Group. D.L. DeMets: Consultant; Self; Actelion Pharmaceuticals US, Inc., AstraZeneca, Boston Scientific, Bristol-Myers Squibb, DalCor Pharmaceuticals, Intercept Pharmaceuticals, Inc., Medtronic. O. Bengtsson: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M. Sjöstrand: Employee; Self; AstraZeneca. P. Jhund: Advisory Panel; Self; Cytokinetics Inc. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Novartis AG. Other Relationship; Self; AstraZeneca. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc. Funding AstraZeneca

Aims In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) and death in patients with HF and reduced ejection fraction. We examined whether this benefit was consistent in relation to background HF therapy. Methods and results In this post hoc analysis, we examined the effect of study treatment in the following yes/no subgroups: diuretic, digoxin, mineralocorticoid receptor antagonist (MRA), sacubitril/valsartan, ivabradine, implanted cardioverter-defibrillating (ICD) device, and cardiac resynchronization therapy. We also examined the effect of study drug according to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA (≥50% and Conclusion The benefit of dapagliflozin was consistent regardless of background therapy for HF.

Renal denervation (RDN) is a potential modality in the treatment of patients with resistant hypertension (RH) and has shown beneficial effect on a variety of cardiovascular surrogate markers. Coronary flow reserve, as assessed by transthoracic Doppler echocardiography (TDE-CFR) is impaired in patients with hypertension and is an independent predictor of cardiac morbidity. However, data on the effect of RDN on TDE-CFR are scarce. The main objective of this study was to assess the effect of RDN on TDE-CFR. Twenty-six consecutive patients with RH (9 female and 17 male; mean age 62 ± 8 years; mean number of antihypertensive drugs 4·2 ± 1·6) underwent bilateral RDN. CFR was assessed at baseline and 6 months after intervention. Mean flow velocity was measured in the left anterior descending artery by transthoracic Doppler echocardiography at baseline and during adenosine infusion (TDE-CFR). Systolic office blood pressure was reduced at follow-up (174 ± 24 versus 162 ± 27 mmHG; P = 0·01). Mean systolic ambulatory blood pressure decreased from 151 ± 21 to 147 ± 18 (P = 0·17). TDE-CFR remained unchanged 6 months after intervention (2·7 ± 0·6 versus 2·7 ± 0·7; P = 0·67). In conclusion, renal denervation was not associated with any changes in regard to coronary flow reserve at 6-month follow-up.

The prognostic role of hypertension on long-term survival after percutaneous coronary intervention (PCI) is limited and inconsistent. We hypothesize that hypertension increases long-term mortality after PCI.We analyzed data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for all consecutive patients admitted coronary care units in Sweden between January 1995 and May 2013 and who underwent PCI due to ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI)/unstable angina (UA) or stable angina pectoris. We used Cox proportional-hazards regression for statistical modelling on complete-case data as well as on imputed data sets. We used interaction test to evaluate possible effect-modulation of hypertension on risk estimates in several pre-specified subgroups: age categories, gender, diabetes, smoking and indication for PCI (STEMI, NSTEMI/UA and stable angina).During the study period, 175,892 consecutive patients underwent coronary angiography due to STEMI, NSTEMI/UA or stable angina. 78,100 (44%) of these had hypertension. Median follow-up was 5.5 years. After adjustment for differences in patient's characteristics, hypertension was associated with increased risk for mortality (HR 1.12, 95% CI 1.09-1.15, p .001). In subgroup analysis, risk was highest in patients less than 65 years, in smokers and in patients with STEMI. The risk was lowest in patients with stable angina (p .001 for interaction test).Hypertension is associated with higher mortality in patients with STEMI, NSTEMI/UA or stable angina who are treated with PCI.

Objective:The objective is to investigate if treatment with thiazides reduces the risk of osteoporotic fractures in hypertensive patients in primary healthcare. Further we aimed to examine the impact of duration of thiazide use, the consequences of discontinuation of treatment, and the possible diff

Background: \ud In patients with type 2 diabetes, inhibitors of sodium–glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.\ud Methods: \ud In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death.\ud Results: \ud Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P

Background Prediction of ischemic cerebral events in patients with heart failure (HF) in the absence of atrial fibrillation (AF) is challenging. Purpose To prospectively test a staged approach to identify patients with HF and sinus rhythm who are at high risk of developing TIA/ischemic stroke (TIA/IS) during the first two years after diagnosis. Methods The analysis is based on patient data reported in the Swedish Heart Failure Register from January 2003 until December 2013. Patients with AF and those treated with anticoagulants were excluded. The study population was categorized in two groups according to left ventricular ejection fraction: LVEF ≤40% and LVEF >40%. Factors associated with TIA/IS were determined by univariate proportional hazard regression. The risk score included: age (1p for 65–74y; 2p for 75–84y; 3p for ≥85y), previous ischemic heart disease (1p), hypertension (1p), diabetes mellitus (1p), TIA/IS (2p), and kidney dysfunction (1p). Two-year hazard ratios with death as competing risk were computed. The probability of observing the outcome was calculated using the cumulative incidence function. Results A total of 16,865 patients (mean age 72.1±13.2y) were included in the study, 39.9% women; 59.7% had LVEF ≤40%. The two-year crude rate of TIA/IS, hemorrhagic stroke, and all-cause mortality were 3.3%, 0.3%, and 26%, respectively. An incremental absolute risk for TIA/IS was observed for patients with LVEF ≤40% and score 1- ≥6: 1.6, 2.3, 3.6, 2.9, 6.3, and 7.1%, respectively. The corresponding HRs with 95% confidence interval (CI) and the patients with 0 points as reference group were: 2.8 (1.1–7.3), 4.0 (1.6–10.1), 6.6 (2.7–16.2), 5.5 (2.2–13.8), 14.4 (5.8–35.9) for score 1- ≥6, where all p-values were less than 0.05 and Wald χ2 for overall model fit In patients with LVEF >40% and score 1–≥6, the absolute TIA/IS risk was: 1.3, 3.1, 3.1, 3.3, 4.6, and 5.3%, respectively. The corresponding HRs with 95% CI and patients with 1 point as reference group was: 2.4 (1.1–5.2), 2.5 (1.2–5.3), 2.7 (1.3–5.7), 3.9 (1.8–8.2); and 4.6 (2.2–9.8), for score 1- ≥6 (all p Conclusion In the current study, a risk score compiling age and specific comorbidity was shown to predict increased risk of TIA/IS, regardless of LVEF, during the first two years after diagnosis in patients with incident HF in sinus rhythm.

Hypertension and fractures related to osteoporosis are major public health problems that often coexist. This study examined the associations between exposure to different antihypertensive drug classes and the risk of hip fracture in hypertensive patients.We included 59 246 individuals, 50 years and older, diagnosed with hypertension during 2001-2008 in the Swedish Primary Care Cardiovascular Database. Patients were followed from 1 January 2006 (or the date of diagnosis of hypertension) until they had their first hip fracture, died, or reached the end of the study on 31 December 2012. Cox proportional hazards models were used to calculate the risk of hip fracture across types of antihypertensive medications, adjusted for age, sex, comorbidity, medications, and socioeconomic factors.In total, 2593 hip fractures occurred. Compared to nonusers, current use of bendroflumethiazide or hydrochlorothiazide was associated with a reduced risk of hip fracture (hazard ratio 0.86; 95% CI 0.75-0.98 and hazard ratio 0.84; 95% CI 0.74-0.96, respectively), as was use of fixed drug combinations containing a thiazide (hazard ratio 0.69; 95% CI 0.57-0.83). Current use of loop diuretics was associated with an increased risk of hip fracture (hazard ratio 1.23; 95% CI 1.11-1.35). No significant associations were found between the risk of hip fracture and current exposure to beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone-receptor blockers or calcium channel blockers.In this large observational study of hypertensive patients, the risk of hip fracture differed across users of different antihypertensive drugs, results that could have practical implications when choosing antihypertensive drug therapy.

Importance: Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes. Objective: To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes. Design, Setting, and Participants: Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Interventions: Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy. Main Outcomes and Measures: The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%. Results: Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction =.80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction =.72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes. Conclusions and Relevance: In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status. Trial Registration: ClinicalTrials.gov Identifier: NCT03036124.

In DAPA-HF, dapagliflozin (10mg qd) compared with placebo, reduced the risk of worsening HF and CV death. It is important to understand whether the effects of dapagliflozin vary according to background HF therapy. Key inclusion criteria: 1) NYHA class II-IV, 2) LVEF ≤40%, and 3) elevated plasma

The aim of this observational cohort study was to investigate blood pressure level and the possibility to reach target blood pressure during concomitant use of NSAID in hypertensive patients.From the Swedish primary care cardiovascular database (SPCCD) a cohort of 5463 patients (2007 to 2008) with at least one prescription of NSAID dispensed 6 months prior to the last blood pressure measurement were included. Clinical data were extracted from computerized medical records and linked to the Prescribed Drug Register. Multivariable logistic regression models were used for analysis.Patients with NSAID usage were younger, more often female, with lower creatinine concentrations, more musculoskeletal diagnosis and less cardiovascular comorbidity compared to patients without dispensed NSAID (p .0001 for all). Regular dose of NSAID was not associated with a decreased possibility to reach target blood pressure. A correlation between the dose of naproxen and an increase in SBP of 7 mm Hg was found. Impairment in renal function did not influence the association between blood pressure control and NSAID (p = .27).In hypertensive patients with concomitant use of NSAID the chance to reach target blood pressure was not impaired. In intermediate and frequent users of NSAID there was a dose response relation with naproxen and SBP which was not found in diclofenac and ibuprofen.

The reasons why women and men are treated with different antihypertensive drugs are not clear. Whether socioeconomic factors influence prescription patterns and blood pressure control differently in women and men has not been investigated. This cross-sectional study performed in a cohort of hypertensive patients from the Swedish Primary Care Cardiovascular Database (SPCCD) examined the influence of educational level, country of birth, gender and concomitant psychiatric disorder on prescription pattern and blood pressure control in 40,825 hypertensive patients. Men were more often than women treated with calcium channel blocker and angiotensin-converting enzyme inhibitor (ACEI), irrespective of education, country of birth and psychiatric disorder. Educational level influenced the prescription pattern to some extent, where the gender differences were reduced in patients with a higher educational level. In women, but not in men, high educational level and concomitant psychiatric disorder were associated with a higher proportion reaching target blood pressure. The predominant use of ACEI and calcium channel blockers in men is not influenced by educational level, country of birth or psychiatric disorder. Thus other explanations must be considered such as gender differences in side effects. Educational level seems to have a greater impact on reaching target blood pressure in women compared with men.

To describe the Swedish Primary Care Cardiovascular Database, SPCCD. Design. Longitudinal data from electronic medical records, linked to national registers. Setting. 48 primary healthcare centres in urban (south-western Stockholm) and rural (Skaraborg) regions in Sweden. Subjects. Patients diagnosed with hypertension 2001-2008.Blood pressure (BP) and impact of retrieval of data on BP levels, clinical characteristics, co-morbidity and pharmacological treatment.The SPCCD contains 74 751 individuals, 56% women. Completeness of data ranged from99% for drug prescriptions to 34% for smoking habits. BP was recorded in 98% of patients during 2001-2008 and in 63% in 2008. Mean BP based on the last recorded value in 2008 was 142 ± 17/80 ± 13 mmHg. Digit preference in BP measurements differed between the two regions, p0.001. Antihypertensive drugs were prescribed in primary healthcare to 88% of the patients in 2008; however, when all prescribers were included 96% purchased their drugs. Cardiovascular co-morbidity and diabetes mellitus were present in 28% and 22%, respectively.This large and representative database shows that there is room for improvement of BP control in Sweden. The SPCCD will provide a rich source for further research of hypertension and its complications.

The efficacy of antihypertensive drug therapy is undisputed, but observational studies show that few patients reach a target blood pressure

The aim of this retrospective study in primary health care was to study gender differences in blood pressure levels in response to treatment of new onset hypertension. Gender difference in blood pressure control and pharmacological treatment was also recorded. A total of 334 women and 332 men aged ≥50 years and80 years at baseline, with blood pressure ≥140 mm Hg systolic and/or ≥90 mm Hg were included. Men were younger, had a higher frequency of type II diabetes mellitus and a higher body mass index compared with women at baseline. There was no difference between women and men in systolic blood pressure (SBP) before or after treatment. Women however had a lower diastolic blood pressure (DBP) before and after intervention and as a result a higher pulse pressure (PP). Approximately 50% of the patients reached target blood pressure (≤140/90 mm Hg) in both women and men. Beta blocker was the most commonly used antihypertensive treatment in both genders, whereas diuretics were predominately used in women. In conclusion; women and men reached target blood pressure to the same extent but with different antihypertensive treatment strategies. Differences at baseline in risk factor pattern may explain the finding.

To review the effects of treating mild to moderate hypertension in women on mortality and cardiovascular morbidity and, further, to examine the evidence for the recommendation to treat women and men equally.A systematic step-by-step review of the literature up to May 2006 identified 80 randomized controlled studies of at least 6 months' duration; 67 were considered to be of satisfactory quality and were selected. Women were included in 59 of the 67 studies.The proportion of women increased from approximately 25% in 1975-1980 to about 40% in 2000-2005 (p0.05). Studies concerning hypertension and concomitant disorders often included fewer women. Results regarding blood pressure reduction were presented separately for women and men in 15 of the 59 studies with female participants, and most of these 15 studies showed no difference in mean blood pressure reduction between women and men. However, two large studies (ALLHAT and VALUE) demonstrated a greater reduction for women on calcium channel blockers. Outcome was reported separately for women and men in 33 studies, and in 28 of them, the outcome analysis was adjusted for sex by regression analysis or interaction by sex in multivariate analysis.No study had as the main objective to compare treatment effect between men and women. Direct scientific evidence from trials of antihypertensive treatment benefit specific to women is weak, but in studies where the analysis was adjusted for gender, the results appear to be similar for women and men. Future studies should be designed to study men and women separately.

There are gender differences in antihypertensive treatment. This study aimed to investigate if gender differences in treatment could be explained by comorbidities. In addition, we aimed to study whether blood pressure control is different in women and men, and whether women interrupt treatment more often with angiotensin–converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) compared with men.This cohort study within the Swedish Primary Care Cardiovascular Database included 40,825 patients with hypertension attending primary health care from 2007 to 2008. Cardiovascular comorbidities, with the exception of heart failure, were more common in men. Women were more often treated with diuretics, and men with ACEI, as were hypertensive patients with diabetes. Comorbidities could not entirely explain gender differences in antihypertensive treatment in a regression model. Women had higher systolic and lower diastolic blood pressure; this was also true in subgroups with cardiovascular comorbidity. Men more often than women were prescribed ACEIs/ARBs and interrupted treatment. Women and men are treated with different antihypertensive drugs, and this is not fully explained by differences in comorbidities. Women have higher systolic blood pressures, irrespective of comorbidity. Men have interrupted treatment more often with ACEIs/ARBs. These gender differences could affect outcome and warrant further investigation.

Objective:To investigate whether treatment with thiazide diuretics reduces the risk of osteoporotic fractures in hypertensive patients in primary health care. Further we aimed to examine the impact of duration of thiazide use, the consequences of discontinuation of use and effect-modifications by ge

The aim of this prospective cohort study was to identify which blood pressure measurement during exercise is the best predictor of future hypertension. Further we aimed to create a risk chart to facilitate the evaluation of blood pressure reaction during exercise testing. A number (n=1047) of exercise tests by bicycle ergometry, performed in 1996 and 1997 were analysed. In 2007-2008, 606 patients without hypertension at the time of the exercise test were sent a questionnaire aimed to identify current hypertension. The response rate was 58% (n=352). During the 10-12 years between exercise test and questionnaire, 23% developed hypertension. The strongest predictors of future hypertension were systolic blood pressure (SBP) before exercise (odds ratios (OR) 1.63 (1.31-2.01) for 10 mm Hg difference) in combination with the increase of SBP over time during exercise testing (OR 1.12 (1.01-1.24) steeper increase for every 1 mm Hg min(-1)). A high SBP before exercise and a steep rise in SBP over time represented a higher risk of developing hypertension. A risk chart based on SBP before exercise, increase of SBP over time and body mass index was created. SBP before exercise, maximal SBP during exercise and SBP at 100 W were significant single predictors of future hypertension and the prediction by maximal SBP was improved by adjusting for time/power at which SBP max was reached during exercise testing. Recovery ratio (maximal SBP/SBP 4 min after exercise) was not predictive of future hypertension.

Objective:Approximately 25% of hypertensive patients >65 years are treated for arthrosis, which is the most common cause of long term use of non-steroidal anti-inflammatory drugs (NSAID). NSAID inhibits prostaglandin synthesis and interacts with the renin angiotensin system. The objective of this st