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There is concern that patients taking renin–angiotensin–aldosterone system inhibitors have an increased risk of Covid-19, because angiotensin-converting enzyme 2 is a receptor for the virus. This study showed no increase in likelihood of a positive Covid-19 test or severe Covid-19 in patients taking any of five common classes of antihypertensive drugs.

In this randomized trial, the discontinuation of renin–angiotensin system inhibitors in patients with advanced chronic kidney disease did not lead to a significant between-group difference in the long-term rate of decline in the eGFR.

In a multicenter placebo-controlled study, patiromer, a nonabsorbable potassium binder, led to a reduction in serum potassium levels in patients with chronic kidney disease and hyperkalemia who were receiving renin–angiotensin–aldosterone system (RAAS) inhibitors. Hyperkalemia is associated with life-threatening cardiac arrhythmias and increased mortality. 1 Patients at the highest risk for hyperkalemia are those with stage 3 or higher chronic kidney disease, with or without diabetes or heart failure, who are being treated with drugs that inhibit renal potassium excretion, particularly inhibitors of the renin–angiotensin–aldosterone system (RAAS). 1 – 4 Outpatient treatment of hyperkalemia is limited by the lack of effective agents. 4 Sodium polystyrene sulfonate and calcium polystyrene sulfonate may cause serious gastrointestinal adverse events 5 – 8 as well as less serious gastrointestinal side effects that may be difficult for patients to tolerate, which together typically limit their . . .

In a randomized trial, 5661 patients with acute myocardial infarction and a reduced left ventricular ejection fraction, pulmonary congestion, or both were assigned to receive either sacubitril–valsartan or ramipril. At a median of 22 months, there was no significant difference between the two groups in the incidence of death from cardiovascular causes or incident heart failure.

The angiotensin receptor–neprilysin inhibitor LCZ696 was compared with the ACE inhibitor enalapril in patients with advanced heart failure. LCZ696 was superior to enalapril in all outcomes. Neprilysin inhibition may replace ACE inhibition for the treatment of heart failure. Angiotensin-converting–enzyme (ACE) inhibitors have been the cornerstone of the treatment for heart failure and a reduced ejection fraction for nearly 25 years, since enalapril was shown to reduce the risk of death in two trials. 1 , 2 Long-term treatment with enalapril decreased the relative risk of death by 16% among patients with mild-to-moderate symptoms. 2 The effect of angiotensin-receptor blockers (ARBs) on mortality has been inconsistent, 3 , 4 and thus, these drugs are recommended primarily for patients who have unacceptable side effects (primarily cough) while receiving ACE inhibitors. Subsequent studies showed that the use of beta-blockers and mineralocorticoid-receptor antagonists, when added to ACE . . .

This population-based case–control study from northern Italy shows that the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 because of a higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors and ARBs affected the risk of Covid-19.

Patients with heart failure with preserved ejection fraction were assigned to receive sacubitril–valsartan or valsartan. At a median of 35 months, there was no significant between-group difference in the composite outcome of total hospitalizations for heart failure or death from cardiovascular causes.

Abstract Aims The objective was to assess the association between angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) prescription at discharge in patients hospitalized for symptomatic lower extremity artery disease (LEAD) and 1-year mortality. Methods and results The COPART registry is a multicentre, prospective, observational, cohort study which includes consecutive patients hospitalized for symptomatic LEAD in four French academic centres. All-cause mortality during a 1-year follow-up after hospital discharge was compared between patients with ARB, patients with ACEI and patients without ARB or ACEI. Analyses were performed using Cox models. As a sensitivity analysis, a propensity score (PS)-matching analysis was carried out. Among 1981 patients, 421 had ARB (21.3%), 766 ACEI (38.7%), and 794 no ACEI/ARB (40.1%) at discharge. During the 1-year follow-up, incidence rates for mortality were 12.6/100 person-years [95% confidence interval (CI) 9.7–16.1] for patients with ARB, 15.8/100 person-years (95% CI 13.4–18.6) for patients with ACEI and 19.8/100 person-years for patients without ACEI/ARB (95% CI 17.2–22.8). In a multivariate Cox model, ARB at discharge was associated with decreased mortality compared with no ACEI/ARB, hazard ratio (HR) 0.68 (95% CI 0.49–0.95), and with ACEI, HR 0.69 (95% CI 0.49–0.97). These results are consistent with those obtained by the Cox analyses in the PS-matched sample: HR 0.68 (95% CI 0.47–0.98) for patients with ARB compared with no ARB. Conclusion Angiotensin receptor blockers at discharge after hospitalization for symptomatic LEAD is associated with a better survival compared with ACEI or no ACEI/ARB.

The rapid spread of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease 2019 (COVID-19). Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for SARS-CoV-2 to enter host target cells. Given that angiotensin receptor blockers (ARBs) and an ACE inhibitor (ACEI) upregulated ACE2 expression in animal studies, the concern might arise regarding whether ARBs and ACEIs would increase the morbidity and mortality of COVID-19. On the other hand, animal data suggested a potential protective effect of ARBs against COVID-19 pneumonia because an ARB prevented the aggravation of acute lung injury in mice infected with SARS-CoV, which is closely related to SARS-CoV-2. Importantly, however, there is no clinical or experimental evidence supporting that ARBs and ACEIs either augment the susceptibility to SARS-CoV-2 or aggravate the severity and outcomes of COVID-19 at present. Until further data are available, it is recommended that ARB and ACEI medications be continued for the treatment of patients with cardiovascular disease and hypertension, especially those at high risk, according to guideline-directed medical therapy based on the currently available evidence.

Uncertainty remains about the optimal monotherapy for hypertension, with current guidelines recommending any primary agent among the first-line drug classes thiazide or thiazide-like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers, in the absence of comorbid indications. Randomised trials have not further refined this choice. We developed a comprehensive framework for real-world evidence that enables comparative effectiveness and safety evaluation across many drugs and outcomes from observational data encompassing millions of patients, while minimising inherent bias. Using this framework, we did a systematic, large-scale study under a new-user cohort design to estimate the relative risks of three primary (acute myocardial infarction, hospitalisation for heart failure, and stroke) and six secondary effectiveness and 46 safety outcomes comparing all first-line classes across a global network of six administrative claims and three electronic health record databases. The framework addressed residual confounding, publication bias, and p-hacking using large-scale propensity adjustment, a large set of control outcomes, and full disclosure of hypotheses tested. Using 4·9 million patients, we generated 22 000 calibrated, propensity-score-adjusted hazard ratios (HRs) comparing all classes and outcomes across databases. Most estimates revealed no effectiveness differences between classes; however, thiazide or thiazide-like diuretics showed better primary effectiveness than angiotensin-converting enzyme inhibitors: acute myocardial infarction (HR 0·84, 95% CI 0·75–0·95), hospitalisation for heart failure (0·83, 0·74–0·95), and stroke (0·83, 0·74–0·95) risk while on initial treatment. Safety profiles also favoured thiazide or thiazide-like diuretics over angiotensin-converting enzyme inhibitors. The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes. This comprehensive framework introduces a new way of doing observational health-care science at scale. The approach supports equivalence between drug classes for initiating monotherapy for hypertension—in keeping with current guidelines, with the exception of thiazide or thiazide-like diuretics superiority to angiotensin-converting enzyme inhibitors and the inferiority of non-dihydropyridine calcium channel blockers. US National Science Foundation, US National Institutes of Health, Janssen Research & Development, IQVIA, South Korean Ministry of Health & Welfare, Australian National Health and Medical Research Council.