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The PARADISE-MI study compared standard treatment with an ACE inhibitor (ramipril) after an acute myocardial infarction with the newer sacubitril/ valsartan combination (so-called ARNI) medication in 5661 patients. Most patients had a reduced cardiac function (40% ejection fraction or less) and in about 50% of patients it was accompanied by complaints of congestion. The expected 15% reduction in primary endpoint cardiovascular death or rehospitalization or extra visits for heart failure was not met after 22 months. The study is characterized by an increased incidence of symptomatic hypotension of 28,3% in the group treated with the ARNI, compared to an incidence of 21,9% in the group treated with the ACE inhibitor. The interpretation of the trial is hampered by the mixed design of prevention and treatment trial for heart failure. A continuing careful approach is advised with ACE inhibitors as first choice in the first week(s) after myocardial infarction.

The PARADISE-MI study compared standard treatment with an ACE inhibitor (ramipril) after an acute myocardial infarction with the newer sacubitril/ valsartan combination (so-called ARNI) medication in 5661 patients. Most patients had a reduced cardiac function (40% ejection fraction or less) and in about 50% of patients it was accompanied by complaints of congestion. The expected 15% reduction in primary endpoint cardiovascular death or rehospitalization or extra visits for heart failure was not met after 22 months. The study is characterized by an increased incidence of symptomatic hypotension of 28,3% in the group treated with the ARNI, compared to an incidence of 21,9% in the group treated with the ACE inhibitor. The interpretation of the trial is hampered by the mixed design of prevention and treatment trial for heart failure. A continuing careful approach is advised with ACE inhibitors as first choice in the first week(s) after myocardial infarction.

Background: Data on the association between quality of heart failure (HF) care and outcomes among patients with incident HF are sparse. We examined the association between process performance measures and clinical outcomes in patients with incident HF with reduced ejection fraction. Methods: Patients with incident HF with reduced ejection fraction (n=10 966) between January 2008 and October 2015 were identified from the Danish HF Registry. Data from public registries were linked. Multivariable regression analyses were used to assess the association between 6 guideline-recommended HF care processes (New York Heart Association assessment, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists, exercise training, and patient education) and all-cause and HF readmission, all-cause and HF hospital days, and mortality within 3 to 12 months after HF diagnosis. The associations were analyzed according to the percentages of all relevant performance measures fulfilled for the individual patient (0%–50% [reference group], >50%–75%, and >75%–100%) and for the individual performance measures. Results: Fulfilling >75% to 100% of the performance measures (n=5341 [48.7%]) was associated with lower risk of all-cause readmission (adjusted hazard ratio, 0.78 [95% CI, 0.68–0.89]) and HF readmission (adjusted hazard ratio, 0.71 [95% CI, 0.54–0.92]), lower use of all-cause hospital days (adjusted mean ratio, 0.73 [95% CI, 0.70–0.76]) and HF hospital days (adjusted mean ratio, 0.79 [95% CI, 0.70–0.89]), and lower mortality (adjusted hazard ratio, 0.42 [95% CI, 0.32–0.53]). A dose-response relationship was observed between fulfilling more performance measures and mortality (adjusted hazard ratio, 0.62 [95% CI, 0.49–0.77] fulfilling >50%–75% of the measures). Fulfilling individual performance measures, except mineralocorticoid receptor antagonist therapy, was associated with lower adjusted all-cause readmission, lower adjusted use of all-cause and HF hospital days, and lower adjusted mortality. Conclusions: Fulfilling more process performance measures was associated with better clinical outcomes in patients with incident HF with reduced ejection fraction.

IntroductionCardiovascular disease is a leading cause of death globally, responsible for nearly 18 million deaths worldwide in 2017. Medications to reduce the risk of cardiovascular events are prescribed based on evidence from clinical trials which explore treatment effects in an indicated sample of the general population. However, these results may not be fully generalisable because of trial eligibility criteria that generally restrict to younger patients with fewer comorbidities. Therefore, evidence of effectiveness of medications for groups underrepresented in clinical trials such as those aged ≥75 years, from ethnic minority backgrounds or with low kidney function may be limited.Using individual anonymised data from the Ongoing Telmisartan Alone and the Ramipril Global Endpoint Trial (ONTARGET) trial, in collaboration with the original trial investigators, we aim to investigate clinical trial replicability within a real-world setting in the area of cardiovascular disease. If the original trial results are replicable, we will estimate treatment effects and risk in groups underrepresented and excluded from the original clinical trial.Methods and analysisWe will develop a cohort analogous to the ONTARGET trial within the Clinical Practice Research Datalink between 1 January 2001 and 31 July 2019 using the trial eligibility criteria and propensity score matching. The primary outcome is a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalisation for congestive heart failure. If results from the cohort study fall within pre-specified limits, we will expand the cohort to include under represented and excluded groups.Ethics and disseminationEthical approval has been granted by the London School of Hygiene & Tropical Medicine Ethics Committee (Ref: 22658). The study has been approved by the Independent Scientific Advisory Committee of the UK Medicines and Healthcare Products Regulatory Agency (protocol no. 20_012). Access to the individual patient data from the ONTARGET trial was obtained by the trial investigators. Findings will be submitted to peer-reviewed journals and presented at conferences.

Arterial hypertension is the most important contributor to the global burden of disease; however, disease control remains poor. Although the diagnosis of hypertension is still based on office blood pressure, confirmation with out-of-office blood pressure measurements (ie, ambulatory or home monitoring) is strongly recommended. The definition of hypertension differs throughout various guidelines, but the indications for antihypertensive therapy are relatively similar. Lifestyle adaptation is absolutely key in non-pharmacological treatment. Pharmacologically, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, and diuretics are the first-line agents, with advice for the use of single-pill combination therapy by most guidelines. As a fourth-line agent, spironolactone should be considered. The rapidly evolving field of device-based therapy, especially renal denervation, will further broaden therapeutic options. Despite being a largely controllable condition, the actual rates of awareness, treatment, and control of hypertension are disappointingly low. Further improvements throughout the process of patient screening, diagnosis, treatment, and follow-up need to be urgently addressed.

ObjectiveWe examined temporal heart failure (HF) prescription patterns in a large representative sample of real-world patients in the UK, using electronic health records (EHR).MethodsFrom primary and secondary care EHR, we identified 85 732 patients with a HF diagnosis between 2002 and 2015. Almost 50% of patients with HF were women and the median age was 79.1 (IQR 70.2–85.7) years, with age at diagnosis increasing over time.ResultsWe found several trends in pharmacological HF management, including increased beta blocker prescriptions over time (29% in 2002–2005 and 54% in 2013–2015), which was not observed for mineralocorticoid receptor-antagonists (MR-antagonists) (18% in 2002–2005 and 18% in 2013–2015); higher prescription rates of loop diuretics in women and elderly patients together with lower prescription rates of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, beta blockers or MR-antagonists in these patients; little change in medication prescription rates occurred after 6 months of HF diagnosis and, finally, patients hospitalised for HF who had no recorded follow-up in primary care had considerably lower prescription rates compared with patients with a HF diagnosis in primary care with or without HF hospitalisation.ConclusionIn the general population, the use of MR-antagonists for HF remained low and did not change throughout 13 years of follow-up. For most patients, few changes were seen in pharmacological management of HF in the 6 months following diagnosis.

Hypertension is a common clinical problem in patients with cancer. This is explained by its high prevalence in the general population, by the improvement in life expectancy in oncology patients thanks to the progress of anti-cancer therapies, but also by cancer therapy, which is sometimes burdened with cardiovascular toxicity. Early detection of hypertension and proper management are crucial to ensure the continuation of oncology treatment and to protect patients from the consequences of hypertension. Renin-angiotensin system blockers and calcium channel blockers are the first-line treatments.

Resumo: O sacubitril/valsartan (LCZ696) é um complexo supramolecular de sal de sódio do pró‐fármaco sacubitril, inibidor da neprilisina, e do valsartan, um antagonista dos recetores da angiotensina (ARB), administrado por via oral, recentemente aprovado no tratamento da insuficiência crónica (classes II‐IV NYHA) com fração de ejeção reduzida (IC‐FER). A inibição neuro‐hormonal é um elemento central no tratamento da insuficiência cardíaca. No entanto, os benefícios obtidos com o aumento de outros sistemas, tais como os péptidos natriuréticos, foram muito parcelares (e inconsistentes). O desenvolvimento do sacubitril/valsartan e os resultados do PARADIGM‐HF mudaram a situação e abriram uma alternativa no tratamento da insuficiência cardíaca crónica. O PARADIGM‐HF foi um grande estudo prospetivo aleatorizado, com dupla ocultação, que demonstrou que a morbimortalidade na insuficiência cardíaca pode ser melhorada com o sacubitril/valsartan, com redução significativa da morte cardiovascular ou da hospitalização por agravamento da insuficiência cardíaca. O sacubitril/valsartan foi também superior ao enalapril na redução da mortalidade total e na limitação da progressão da insuficiência cardíaca. O novo ARNi foi geralmente bem tolerado, sem incremento dos eventos adversos potencialmente fatais (apesar da maior incidência de hipotensão sintomática, mas com uma baixa ocorrência de angioedema). Por essa razão, o sacubitril/valsartan deve substituir o ACEi (ou o ARB) no tratamento da IC‐FER, afirmação já expressa em muitas das novas recomendações terapêuticas. Abstract: Sacubitril/valsartan (LCZ696), a supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, was recently approved in the EU and the USA for the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF) (NYHA class II‐IV). Inhibition of chronically activated neurohormonal pathways (the renin‐angiotensin‐aldosterone system [RAAS] and sympathetic nervous system [SNS]) is central to the treatment of chronic HFrEF. Furthermore, enhancement of the natriuretic peptide (NP) system, with favorable cardiovascular (CV) and renal effects in HF, is a desirable therapeutic goal to complement RAAS and SNS blockade. Sacubitril/valsartan represents a novel pharmacological approach that acts by enhancing the NP system via inhibition of neprilysin (an enzyme that degrades NPs) and by suppressing the RAAS via AT1 receptor blockade, thereby producing more effective neurohormonal modulation than can be achieved with RAAS inhibition alone. In the large, randomized, double‐blind PARADIGM‐HF trial, replacement of an angiotensin‐converting enzyme inhibitor (ACEI) (enalapril) with sacubitril/valsartan resulted in a significant improvement in morbidity and mortality in patients with HFrEF. Sacubitril/valsartan was superior to enalapril in reducing the risk of CV death or HF hospitalization (composite primary endpoint) and all‐cause death, and in limiting progression of HF. Sacubitril/valsartan was generally well tolerated, with a comparable safety profile to enalapril; symptomatic hypotension was more common with sacubitril/valsartan, whereas renal dysfunction, hyperkalemia and cough were less common compared with enalapril. In summary, sacubitril/valsartan is a superior alternative to ACEIs/ARBs in the treatment of HFrEF, a recommendation that is reflected in many HF guidelines. Palavras‐chave: Sacubitril/valsartan, Insuficiência cardíaca, Inibição da neprilisina, Antagonista do recetor da angiotensina‐inibidor da neprilisina, PARADIGM‐HF, Keywords: Sacubitril/valsartan, Heart failure, Neprilysin inhibition, Angiotensin receptor‐neprilysin inhibitor, PARADIGM‐HF

Aims The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin–angiotensin–aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. Methods and results We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort). The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = –0.17, P = 0.002) and ARB use (estimate = –0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. Conclusion In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.

International audience; Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.

Blockade of the renin-angiotensin-aldosterone system (RAAS) is a standard therapeutic intervention in diabetic patients with chronic kidney disease (CKD). Concomitant mineralocorticoid receptor blockade has been studied as a novel approach to further slow down CKD progression. We used PubMed and EMBASE databases to search for relevant literature. We included in our review eight studies in patients of at least 18 years of age, with a diagnosis of type 1 or type 2 diabetes mellitus and diabetic nephropathy, under an angiotensin converting enzyme inhibitor (ACEI) and/or an angiotensin II receptor blocker (ARB) as standard treatment. A subset of patients in each study also received a mineralocorticoid receptor blocker (MRB) (either spironolactone or eplerenone) in addition to standard treatment. Combined treatment with a mineralocorticoid receptor blocker further reduced albuminuria by 23 to 61% compared with standard treatment. Estimated glomerular filtration rate values upon study completion slightly decreased under combined treatment. Blood pressure levels upon study completion were significantly lower with combined treatment in three studies. Hyperkalemia prevalence increased in patients under combined treatment raising dropout rate up to 17%. Therefore, combined treatment by an ACEI/ARB and a MRB may further decrease albuminuria in diabetic nephropathy. This effect may be due to the specific properties of the MRB treatment. Clinicians should regularly check potassium levels because of the increased risk of hyperkalemia. Available evidence should be confirmed by an adequately powered comparative trial of the standard treatment (ACEI or ARB) versus combined treatment by an ACEI/ARB and a MRB.

Aim: To describe the prevalence of hypertension in care home residents, its treatment, change in treatment over time, and the achievement of blood pressure (BP) control. Method: The PubMed, Cochrane, Embase, and PsychINFO databases were searched for observational studies involving care home residents with a diagnosis of hypertension. The search was limited to English language articles involving adults and humans published from 1990 onward. Abstracts and titles were reviewed with eligible articles read in full. Bibliographies were examined for further relevant studies. The final selection of studies was then analyzed and appraised. Results: Sixteen articles were identified for analysis, of which half were studies carried out in the United States. The prevalence of hypertension in care home residents was 35% (range 16%e71%); 72% of these were on at least 1 antihypertensive (mean 1.5 antihypertensives per individual), with diuretics being the most common. The prevalence of hypertension in study populations was greater in more recent studies (P ¼ .004). ACEi/ARBs (P ¼ .001) and b-blockers (P ¼ .04) were prescribed more frequently in recent studies, whereas use of calcium-channel blockers and diuretics remained unchanged over time. The number of antihypertensives prescribed per patient was higher (correlation 0.332, P ¼ .009), whereas fewer patients achieved target BP (correlation 0.671, P ¼ .099) in more recent studies. Conclusion: Hypertension is common in care home residents and is commonly treated with antihypertensive drugs, which were prescribed more frequently in more recent studies but with no better BP control. These studies indicate a tendency toward increasing polypharmacy over time, with associated risk of adverse events, without demonstrable benefit in terms of BP control. Copyright 2014 - American Medical Directors

To investigate the association of antihypertensive medications with optic disc structure by blood pressure (BP) level, in nonglaucoma subjects.Cross-sectional, population-based study.A subset of Thessaloniki Eye Study participants was included in this study. Subjects were interviewed for medical history and underwent extensive ophthalmic examination, BP measurement, and optic disc imaging with the Heidelberg retinal tomograph. Subjects treated for hypertension were grouped in the following groups: (1) angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blockers; (2) beta blockers and/or calcium-channel blockers; (3) diuretics alone or combined with others; and (4) other combinations. Cup size and cup-to-disc (C/D) ratio in the above groups were compared with the untreated group, using regression models. Analyses were rerun for subjects with systolic BP (SBP)140 mm Hg, SBP≥140 mm Hg, diastolic BP (DBP)90 mm Hg, and DBP≥90 mm Hg.Among 232 subjects, 131 were receiving antihypertensive medications. In subjects with DBP90 mm Hg, all medications groups were associated with larger cup size and higher C/D ratio compared with the untreated group. Results were similar in subjects with SBP140 mm Hg, with the exception of the beta blockers and/or calcium-channel blockers group. None of the medications groups were associated with the Heidelberg retinal tomograph parameters in those with DBP≥90 mm Hg or SBP≥140 mm Hg.All classes of antihypertensive medications were associated with larger cup size and higher C/D ratio in subjects with either DBP90 mm Hg or SBP140 mm Hg. These results suggest that there is no specific medication-related effect on optic disc structure, and the associations found are mediated through the hypotensive effect of antihypertensive medications.

OBJECTIVE: Angiotensin receptor blockers (ARBs) have been suggested to reduce inflammation in randomized controlled trials. We assessed the association between ARBs and inflammatory markers in a general population setting. METHODS: This is a population-based prospective study conducted in Lausanne, Switzerland. Baseline data from 933 participants on antihypertensive drugs (424 on ARBs) was collected in 2003-2006. Follow-up data from 1120 participants (572 on ARBs) was collected in 2009-2012. C-reactive protein (CRP), interleukins 1β and 6 and tumor necrosis factor alpha (TNF-α) were assessed and categorized in quartiles. RESULTS: At baseline, no differences were found between participants taking or not taking ARBs for all inflammatory markers studied, and this association persisted after multivariate adjustment: odds ratios (ORs) and (95% confidence interval) for being in the highest quartile of interleukin-1β, interleukin-6, TNF-α and CRP for participants on ARB compared to participants not on ARB were 1.23 (0.89-1.70), 1.26 (0.93-1.70), 1.14 (0.85-1.53) and 1.27 (0.96-1.69) respectively (P > 0.05). These findings were further replicated in the follow-up study: OR and (95% CI) of 1.10 (0.78-1.55), 0.87 (0.64-1.19), 0.83 (0.61-1.14) and 0.91 (0.68-1.22) for interleukin-1β, interleukin-6, TNF-α and CRP respectively (P > 0.05). Finally, no effect of ARBs was found when comparing participants who received ARBs throughout the 5.4-year follow-up with participants on other antihypertensive drugs: OR and (95% CI) of 0.93 (0.61-1.42), 0.80 (0.54-1.17), 0.86 (0.59-1.25) and 0.95 (0.67-1.35) for interleukin-1β, interleukin-6, TNF-α and CRP respectively (P > 0.05). CONCLUSION: ARBs are not associated with reduced levels of inflammatory markers in the general population.

Background— Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. Methods and Results— We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74–0.94; P =0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52–0.85; P =0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P P =0.005), to receive intravenous positive inotropic agents (31% risk reduction, P P =0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro–B-type natriuretic peptide and troponin) versus enalapril. Conclusions— Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01035255.

BackgroundCoronary atherothrombosis due to atherosclerotic plaque rupture or erosion is frequently associated with acute coronary syndromes (ACS). Significant efforts have been made to elucidate the pathophysiological mechanisms underlying acute coronary events. Materials and methodsThis narrative review is based on the material searched for and obtained via PubMed up to August 2014. The search terms we used were as follows: angiotensin, acute coronary syndromes, acute myocardial infarction' in combination with atherosclerosis, vulnerability, clinical trial, ACE inhibitors, inflammation'. ResultsAmong several regulatory components, the renin-angiotensin system (RAS) was shown as a key pathway modulating coronary atherosclerotic plaque vulnerability. Indeed, these molecules are involved in all stages of atherogenesis. Classically, the RAS is composed by a series of enzymatic reactions leading to the angiotensin (Ang) II generation and activity. However, the knowledge of RAS has expanded and become more complex. The discovery of novel components and their functions has revealed additional pathways that contribute to or counterbalance the actions of Ang II. In this review, we discussed on recent findings concerning the role of different angiotensin peptides in the pathophysiology of ACS and coronary atherothrombosis, exploring the link between these molecules and atherosclerotic plaque vulnerability. ConclusionsTreatments selectively targeting angiotensins (including Mas and AT2 agonists, ACE2 recombinant, or Ang-(1-7) and almandine in oral formulations) have been tested in animal studies or in small human subgroups, expanding the perspective in the ACS prevention. These novel strategies, especially in the counter-regulatory axis ACE2/Ang-(1-7)/Mas, might be promising to reduce plaque vulnerability and inflammation.

International audience; BACKGROUND: We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy. METHODS: In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years. RESULTS: The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P\textless0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P\textless0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years. CONCLUSIONS: In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495.).

The angiotensin AT2-receptor mediates tissue protective actions. Its regenerative potential has been tested in multiple disease models including models of myocardial infarction. These studies used different experimental approaches in order to detect AT2-receptor-related effects such as AT2-receptor deficiency or overexpression, treatment with an AT1-receptor blocker leading to indirect stimulation of the unopposed AT2-receptor, or studies using AT2-receptor agonists. It is a common finding in these studies that the AT2-receptor improves cardiac function in the early phase post-MI, and that this effect is preserved over periods of up to four months. Depending on the experimental protocol, the AT2R also attenuates post-MI left ventricular remodeling or protects the heart from early left ventricular thinning and rupture. In combination with AT1-receptor blockade or deficiency, post-MI cardiac hypertrophy is reduced. This article reviews studies on the role of the AT2-receptor in myocardial infarction with an emphasis on the most recent data obtained in studies using AT2-receptor agonists.

Aims: Although active-controlled trials with renin–angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos.\ud \ud Methods and results: We used the treatment-arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) as the reference trial for comparison of an ACE inhibitor to placebo and the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity-Alternative trial (CHARM-Alternative) as the reference trial for comparison of an ARB to placebo. The hazard ratio of LCZ696 vs. a putative placebo was estimated through the product of the hazard ratio of LCZ696 vs. enalapril (active-control) and that of the historical active-control (enalapril or candesartan) vs. placebo. For the primary composite outcome of cardiovascular death or heart failure hospitalization in PARADIGM-HF, the relative risk reduction with LCZ696 vs. a putative placebo from SOLVD-T was 43% (95%CI 34–50%; P < 0.0001) with similarly large effects on cardiovascular death (34%, 21–44%; P < 0.0001) and heart failure hospitalization (49%, 39–58%; P < 0.0001). For all-cause mortality, the reduction compared with a putative placebo was 28% (95%CI 15–39%; P < 0.0001). Putative placebo analyses based on CHARM-Alternative gave relative risk reductions of 39% (95%CI 27–48%; P < 0.0001) for the composite outcome of cardiovascular death or heart failure hospitalization, 32% (95%CI 16–45%; P < 0.0001) for cardiovascular death, 46% (33–56%; P < 0.0001) for heart failure hospitalization, and 26% (95%CI 11–39%; P < 0.0001) for all-cause mortality.\ud \ud Conclusion: These indirect comparisons of LCZ696 with a putative placebo show that the strategy of combined angiotensin receptor blockade and neprilysin inhibition led to striking reductions in cardiovascular and all-cause mortality, as well as heart failure hospitalization. These benefits were obtained even though LCZ696 was added to comprehensive background beta-blocker and mineralocorticoid receptor antagonist therapy.

OBJECTIVES: Despite a broad and efficient pharmacological antihypertensive armamentarium, blood pressure (BP) control is suboptimal and heterogeneous throughout Europe. Recent representative data from Switzerland are limited. The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerland in accordance with current guidelines. The influence of risk factors, target organ damage and medication on BP levels and control was also evaluated.METHODS : A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerland. 281 randomly selected physicians provided data on 5 consecutive hypertensive patients attending their practices for BP follow-up. Data were anonymously collected on demographics, comorbidities and current medication, and BP was recorded. Subsequent modification of pharmacological antihypertensive therapy was assessed.RESULTS : Data from 1376 patients were available. Mean age was 65 +/- 12 years, 53.9% were male subjects. 26.4% had complicated hypertension. Overall, BP control (

Background It is well known that inappropriate or exaggerated activity of the renin-angiotensin system might contribute to the development of systemic hypertension with consequent organ injury and associated increased risk of acute cardiovascular (CV) diseases. This review will discuss evidence form basic research and clinical studies, investigating the efficacy of angiotensin II receptor blockers (ARBs) in the management of acute coronary syndromes (ACS). Materials and methods This narrative review is based on the material found on MEDLINE and PubMed up to June 2013. We looked for the terms ‘angiotensin, AT1 receptor, ACE inhibitors’ in combination with ‘acute coronary syndromes, acute myocardial infarction, pathophysiology’. Results Preclinical studies showed relevant protective effects of ARBs to reduce adverse cardiac remodelling in animal models of acute cardiac ischaemia. However, although recommended in Consensus guidelines as a good alternative to angiotensin-converting enzyme inhibitors (ACEIs), clinical studies did not confirm a superior efficacy of the ARBs as compared to ACEIs. As a matter of fact for some authors, these drugs might potentially have deleterious effects increasing the CV risk. Conclusions Emerging evidence from clinical trials suggests that the use of ARBs in ACS might be controversial, and caution should be used for their clinical use to replace ACEIs in ACS.