Angiotensin-Converting Enzyme Inhibitors

AimsThe aims of this study were to assess prescription patterns, dosages, discontinuation rates, and association with prognosis of conventional heart failure medications in patients with transthyretin cardiac amyloidosis (ATTR-CA).Methods and resultsA retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the National Amyloidosis Centre between 2000 and 2022 identified 2371 patients with ATTR-CA. Prescription of heart failure medications was greater among patients with a more severe cardiac phenotype, comprising beta-blockers in 55.4%, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin II receptor blockers (ARBs) in 57.4%, and mineralocorticoid receptor antagonists (MRAs) in 39.0% of cases. During a median follow-up of 27.8 months (interquartile range 10.6-51.3), 21.7% had beta-blockers discontinued, and 32.9% had ACEi/ARBs discontinued. In contrast, only 7.5% had MRAs discontinued. A propensity score-matched analysis demonstrated that treatment with MRAs was independently associated with a reduced risk of mortality in the overall population [hazard ratio (HR) 0.77 (95% confidence interval (CI) 0.66-0.89), P 40% [HR 0.75 (95% CI 0.63-0.90), P = .002]; and treatment with low-dose beta-blockers was independently associated with a reduced risk of mortality in a pre-specified subgroup of patients with a LVEF ≤40% [HR 0.61 (95% CI 0.45-0.83), P = .002]. No convincing differences were found for treatment with ACEi/ARBs.ConclusionConventional heart failure medications are currently not widely prescribed in ATTR-CA, and those that received medication had more severe cardiac disease. Beta-blockers and ACEi/ARBs were often discontinued, but low-dose beta-blockers were associated with reduced risk of mortality in patients with a LVEF ≤40%. In contrast, MRAs were rarely discontinued and were associated with reduced risk of mortality in the overall population; but these findings require confirmation in prospective randomized controlled trials.

Hypertension is a major risk factor for heart attack, produce atherosclerosis (hardening of the arteries), congestive heart failure, stroke, kidney infection, blindness, end-stage renal infection, and cardiovascular diseases. Many mechanisms are involved in causing hypertension, i.e., via calcium channels, alpha and beta receptors, and the renin-angiotensin system (RAS). RAS has an important role in blood pressure control and is also involved in the metabolism of glucose, homeostasis, and balance of electrolytes in the body. The components of RAS that are involved in the regulation of blood pressure are angiotensinogen, Ang I (angiotensin I), Ang II (angiotensin II), ACE (angiotensin-converting enzyme), and ACE 2 (angiotensin-converting enzyme 2). These components provide for relevant therapeutic targets for the treatment of hypertension, and various drugs are commercially available that target individual components of RAS. Angiotensin receptor blockers (ARBs) and ACE inhibitors are the most popular among these drugs. ACE is chosen in this review as it makes an important target for blood pressure control because it converts Ang I into Ang II and also acts on the vasodilator, bradykinin, to degrade it into inactive peptides. This review highlights various aspects of blood pressure regulation in the body with a focus on ACE, drugs targeting the components involved in regulation, their associated side effects, and a need to shift to alternative therapy for putative hypertension treatment in the form of bioactive peptides from food.

BackgroundHyperkalemia (HK) is a barrier to optimization of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy in heart failure (HF) and chronic kidney disease (CKD). We investigated cardiorenal risk associated with changes in RAASi regimen after an episode of HK in patients with HF and/or CKD.MethodsThis observational study utilized data from hospital records, claims, and health registers from the US (Optum's de-identified Market Clarity Data) and Japan (Medical Data Vision). Included patients had an index episode of HK between July 2019 and September 2021 (US), or May 2020 and September 2021 (Japan), with prior diagnosis of HF or CKD (stage 3 or 4), and RAASi use. Risk of a cardiorenal composite outcome (HF emergency visit, HF hospitalization, or progression to end-stage kidney disease) was determined in patients who discontinued RAASi, down-titrated their dose by > 25%, or maintained or up-titrated their dose following the HK episode.ResultsA total of 15,488 and 6020 patients were included from the US and Japan, respectively. Prior to the episode of HK, 59% (US) and 27% (Japan) of patients had achieved > 50% target RAASi dose. Following the episode of HK, 33% (US) and 32% (Japan) of patients did not fill a new RAASi prescription. Risk of the cardiorenal outcome at 6 months was higher in patients who discontinued or down-titrated versus maintained or up-titrated RAASi treatment both in the US (17.5, 18.3, and 10.6%; p ConclusionHK-related RAASi discontinuation or down-titration was associated with higher risk of cardiorenal events versus maintained or up-titrated RAASi.

BackgroundAngiotensin-converting enzyme (ACE) inhibitors are widely used antihypertensive agents with proven cardioprotective effects. Previous mechanistic and clinical studies have suggested that ACE inhibitor therapy may slow disease progression and reduce mortality in idiopathic pulmonary fibrosis (IPF).Research questionDoes ACE inhibitor use associate with reduced all-cause mortality in a real-world population of patients with IPF, and if so, is the association also present in patients with COPD?Study design and methodsA retrospective analysis was conducted by using electronic health records from the Clinical Practice Research Datalink GP Online Database (2019), linked with Hospital Episode Statistics Admitted Patient Care and Office for National Statistics death registration data. Patients with IPF and COPD were stratified based on ACE inhibitor use (defined as ≥ 3 prescriptions within the 5 years preceding diagnosis) and matched by age, sex, and smoking history using propensity score matching. Multivariable Cox regression analyses were performed, adjusting for age, sex, BMI, smoking status, indices of multiple deprivation, diabetes mellitus, chronic kidney disease, and common cardiovascular comorbidities. In the IPF cohort, competing risk analysis was used to account for cause-specific mortality.ResultsThe study included 3,579 patients with IPF and matched COPD control participants (mean age, 74 years; 36% female). Among the IPF cohort, 1,328 (37%) were ACE inhibitor users, compared with 1,061 (30%) among patients with COPD. ACE inhibitor use was associated with improved survival, independent of coexisting comorbidities, in patients with IPF (hazard ratio, 0.82; 95% CI, 0.75-0.91; P ≤ .001), but a similar association was not found in patients with COPD (hazard ratio, 1.09; 95% CI, 0.96-1.23; P = .180).InterpretationIn this study, ACE inhibitor therapy was independently associated with reduced all-cause mortality in IPF but not in COPD. Prospective trials are warranted to confirm these findings in IPF populations.