The Potential Effects of ACE Inhibitors on the Severity of Periodontal Disease-Related Attachment Loss: An Observational, Cross-Sectional Comparative Study

Prognostic Impact of Angiotensin-Converting Enzyme Inhibitor Therapy in Diastolic Heart Failure

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The current British Hypertension Society (BHS) Guidelines for the management of Hypertension run to an impressive 46 pages.1 The Quick Reference Guide on management of hypertension in adults in primary care published by the National Institute of Health and Clinical Excellence (NICE) in June 2006 is shorter at 11 pages.2 Both documents give essentially the same message about thresholds, treatments, and targets for hypertensive patients with the NICE guide providing easy to follow, colourful flow diagrams. By definition clinical guidelines need to be clear and user-friendly but I worry that important and subtle messages may be lost completely in the process. A case in point is the management of hypertension in young women of childbearing age. In the NICE Quick Reference Guide only one line mentions this group saying that beta blockers should be avoided in women of childbearing age. There is no mention of why and no reference to the potential dangers of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) should these women become pregnant. Research emerging in the early 1990s indicated a causative association between the use of ACE inhibitors during pregnancy and the development of severe fetal abnormalities. A significantly increased incidence of oligohydramnios, neonatal renal failure, pulmonary hypoplasia, calvarial hypoplasia, and fetal death were reported. These effects are thought to be the result of hypoperfusion of the fetal kidneys during development.3 The increased risk of fetal abnormalities was initially thought to be limited to women receiving ACE inhibitor therapy in the second and third trimesters of pregnancy. However, a more recent study has suggested a significantly increased risk (>2.7) of major congenital malformations in women receiving ACE inhibitor therapy in the first trimester of pregnancy.4 A higher incidence of fetal abnormalities in the offspring of women taking ARBs during pregnancy has also been noted.5 Current BHS guidelines recommend ACE inhibitors as first-line agents for younger, non-black patients but advise that these agents should be avoided in women who wish to become pregnant. The recommendations also state that ACE inhibitors and ARBs should be discontinued immediately if a woman were to become pregnant while receiving treatment with either agent. The Quick Reference NICE guidelines suggest beta blockers may have a role in younger women but do not specify why.2 Despite their known adverse effects, recent US data shows that 4.4% of women of childbearing age (15–44 years) take ACE inhibitors, reflecting an 83% increase in use from 1995–2002.6 In addition, a UK poll suggests that 40% of pregnancies are unplanned, with over half of these due to lack of contraception.7 At the Hypertension Clinic, University Hospital Birmingham we recently investigated the number of women of childbearing age (16–45 years), who had been prescribed ACE inhibitors or ARBs in primary care before referral.8 In addition, contraceptive use by these women was evaluated to assess whether adequate precautions were being taken to prevent pregnancy in these at-risk patients. A cohort of female patients aged 16–45 years was identified from approximately 1500 new referrals from January 2004 to October 2006, excluding those not taking antihypertensive medication. Contraceptive status was established where possible. Forty-seven of 101 (47%) women aged 16–45 years were taking an ACE inhibitor (n = 35) an ARB (n = 11) or both (n = 1) of whom 26 (55%) were aged 16–40 years. In this younger group, eight were using no contraception and three were using barrier methods only. In other words, one-quarter of women in the study were taking these agents and were aged 40 years or less; of these, many were not using reliable contraception. The study identifies a worrying trend to use ACE inhibitors or ARBs in younger women who are at risk of poor perinatal outcomes if they become pregnant. On the basis of this small study and my own clinical experience I feel that the BHS and NICE guidelines may put younger women at risk if doctors are unaware of potential fetotoxic and teratogenic consequences of prescribing ACE inhibitors and ARBs. When I give talks to GPs and hospital doctors, several colleagues confirm that they were previously unaware of such an association. A final point that the study highlighted was the surprising number of young women who were taking antihypertensives in the first place. This brings me on to thresholds for intervention, white coat hypertension, and appropriateness of treatment in this very low-risk group: important subjects for another Viewpoint, perhaps.

Gut Microbiota: Friends or Foes for Blood Pressure-Lowering Drugs.

Treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) during pregnancy can cause severe foetal abnormalities. This study aimed to identify the proportion of women of childbearing age taking ACE inhibitors or ARBs on referral to a tertiary Hypertension Clinic. Retrospective cohort study. A cohort of female patients aged 16-45 years was identified from approximately 1500 new referrals from January 2004 to October 2006, excluding those not taking antihypertensive medication. ACE inhibitors and ARBs were grouped together for the purposes of the study. Contraceptive status was established where possible. Forty seven of 101 (47%) women aged 16-45 years were taking an ACE inhibitor (35) an ARB (11) or both (1) of whom 26 (55%) were aged 16-40 years. In this younger group, eight were using no contraception and three were using barrier methods only. Many GPs continue to prescribe ACE inhibitors and ARBs to women of childbearing age. A quarter of women in the study were taking these agents and were 40 years or less; of these many were not using reliable contraception. These women are at risk of foetal malformation and poor perinatal outcomes if they become pregnant. The British Hypertension Guidelines may put younger women at risk if general practitioners are unaware of potential foetotoxic and teratogenic consequences of prescribing ACE inhibitors and ARBs to women of child bearing age.

ACE inhibitors to block MMP-9 activity: New functions for old inhibitors

Dual blockade of the renin‐angiotensin system with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

American Academy of Periodontology Task Force Report on the Update to the 1999 Classification of Periodontal Diseases and Conditions.

Comparative Impacts of ACE (Angiotensin-Converting Enzyme) Inhibitors Versus Angiotensin II Receptor Blockers on the Risk of COVID-19 Mortality.

Treatment with an angiotensin-converting enzyme (ACE) inhibitor benefits many patients with cardiovascular disease. ACE inhibitors are generally assumed to be equally effective, but this has never been fully verified in clinical trials. Studying the association among ACE inhibitors after myocardial infarction demonstrated similarity in clinical outcome and supports a dosage-response relationship. Therefore, for long-term benefits for patients who need treatment with an ACE inhibitor, a focus of treatment at the recommended dosage is most important and not which ACE inhibitor is used. Therapy with angiotensin-converting enzyme (ACE) inhibitors is common after myocardial infarction (MI). Given the lack of randomized trials comparing different ACE inhibitors, the association among ACE inhibitors after MI in risk for mortality and reinfarction was studied. Patients hospitalized with first-time MI (n = 16,068) between 1995 and 2002, who survived at least 30 days after discharge and claimed at least one prescription of ACE inhibitor, were identified using nationwide administrative registries in Denmark. Adjusted Cox regression analysis demonstrated no differences in risk for all-cause mortality, but patients using captopril had higher risk of reinfarction (hazard ratio 1.18, 95% confidence interval 1.05, 1.34). However, following adjustment for differences in used dosages, all ACE inhibitors had similar clinical efficacy. Risk of all-cause mortality: trandolapril (reference) 1.00, ramipril 0.97 (0.89, 1.05), enalapril 1.04 (0.95, 1.150), captopril 0.95 (0.83, 1.08), perindopril 0.98 (0.84, 1.15) and other ACE inhibitors or angiotensin II receptor blockers (ARB) 1.06 (0.94, 1.19). Reinfarction: trandolapril (reference) 1.00, ramipril 0.98 (0.89, 1.08), enalapril 1.04 (0.92, 1.17), captopril 1.05 (0.89, 1.25), perindopril 0.96 (0.81, 1.14) and other ACE inhibitors or ARB 0.99 (0.86, 1.14). Furthermore, the association between ARBs and clinical events was similar to ACE inhibitors (trandolapril reference): all-cause mortality 0.99 (0.84, 1.16) and recurrent MI 0.99 (0.83, 1.19). Our results suggest a class effect among ACE inhibitors when used in comparable dosages. Focus on treatment at the recommended dosage is therefore most important, and not which ACE inhibitor is used.

Section 7: Heart Failure in Patients With Left Ventricular Systolic Dysfunction

Plasma Angiotensin Peptide Profiling and ACE (Angiotensin-Converting Enzyme)-2 Activity in COVID-19 Patients Treated With Pharmacological Blockers of the Renin-Angiotensin System.

ACE inhibitors in hemodialysis patients: Does survival improve?

Background/Aims: Some angiotensin converting enzyme (ACE) inhibitors are efficiently removed from circulation by hemodialysis (‘high dialyzability'), whereas others are not (‘low dialyzability'). In patients receiving hemodialysis, this may influence the effectiveness of ACE inhibitors. Methods: Using linked healthcare databases we identified older patients receiving chronic hemodialysis who filled new ACE inhibitor prescriptions. The low dialyzability group (n = 3,369) included fosinopril and ramipril. The high dialyzability group (n = 5,974) included enalapril, lisinopril, and perindopril. The primary outcome was all-cause mortality within 180 days of first ACE inhibitor prescription. Results: There were 361 deaths among 5,974 patients (6.0%) prescribed with low dialyzability ACE inhibitors and 179 deaths among 3,369 patients (5.3%) prescribed with high dialyzability ACE inhibitors (relative risk 1.1, 95% CI 0.9-1.3, p = 0.6). Conclusion: In this study of older patients receiving hemodialysis, the dialyzability of ACE inhibitors was not associated with mortality or cardiovascular outcomes.