Risk estimates were similar for men and women and across specific ARBs and did not increase with increasing duration of exposure. Switch the patient to the fully covered ARB at a therapeutically appropriate dose as shown below. Clinicians can continue to prescribe ARBs without concern about an excess risk of cancer. Silicone LED Papa Puppy Night Light Touch Sensor Switching Night Lamp, Transform Between Warm White 2700K and White 6500K, Safe SIL+ABS, Sleep Timer Setting for Kids Babies Bedside and Nursery: Amazon.in: Home & Kitchen Tel: +39 02 55033592, Email: … In these analyses, 365 defined daily doses were defined as equivalent to 1 year, and the cumulative received doses were counted starting after the lag period. Using participants' unique personal identification numbers, we linked individual-level information from nationwide registries on filled drug prescriptions, cancer diagnoses, and potential confounders. The odds ratio (OR) and 95% confidence interval (CI) were calculated with binary logistic regression. Figure 2 shows associations between ARB use and cancer subgroups by anatomic site. Published on behalf of the European Society of Cardiology. 20 mg. 40 mg. telmisartan (MICARDIS) 2 . I stay well away from abs now. Kuster GM, Pfister O, Burkard T, Zhou Q, Twerenbold R, Haaf P, Widmer AF, Osswald S. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. https://www.epicentro.iss.it/coronavirus/bollettino/Report-COVID-2019_20_marzo_eng.pdf. Figure 3. Results were similar when ARBs were compared with other antihypertensive drugs in a sensitivity analysis. We included all ARBs (ATC-code C09CA) and ACE-inhibitors (C09AA) in use in Denmark, including combinations with thiazide diuretics (C09DA and C09BA, respectively): losartan, eprosartan, valsartan, irbesartan, candesartan, telmisartan, and olmesartan; and captopril, enalapril, lisinopril, perindopril, ramipril, quinapril, benazepril, fosinopril, trandolapril, and moexipril. This work was supported by a research grant from the Danish Medical Research Council. structural!constraints!! We established a cohort of new users of ARBs and ACE inhibitors, including those who filled a new prescription during the study period. It allows for switching between dynamic holography and dynamic color display, taking advantage of the reversible phase transition of magnesium through hydrogenation and dehydrogenation. In an analysis including >100 000 users of ARBs and >200 000 users of angiotensin-converting enzyme inhibitors, we found no evidence of an increased risk of cancer overall associated with ARB use. In case of a switch from ACE inhibitors to ARBs, it seems reasonable to stop ACE inhibitors and start ARBs the following day at an equivalent dose. So, we’re now choosing between losartan, olmesartan, and telmisartan. Diagnoses of incident cancer were identified via the Danish Cancer Registry,20 which documents all cases of cancer in the country with high completeness and validity20; cancers are classified according to the International Classification of Diseases. The primary outcome measure was risk of incident cancer overall in new users of ARBs compared with new users of ACE inhibitors. The mean duration of ARB and ACE inhibitor use was 2.9 years (SD, 2.2 years) and 2.1 years (SD, 1.9 years), respectively. However, if they later refilled a prescription and fulfilled criteria for use, past users could again be recategorized and contribute person-time to the user group. A design that compares initiators of 2 drugs with shared indications has advantages over a design that uses nonusers as a comparison group, reducing the potential for immortal time bias and balancing the treatment groups with regard to patient characteristics not measured in the available register data,40 in our case, for example, smoking, physical activity, and dietary habits. Because millions of patients use ARBs, monitoring their safety is of immediate clinical importance. A trial of 54 patients, all of whom experienced ACE inhibitor–induced angioedema, was performed to determine the safety of using other antihypertensive medications in … A more conservative definition that did not allow gaps between prescriptions, thereby probably limiting analyses to those with more consistent drug exposure, yielded results very similar to the main analysis. Furthermore, we did not detect increased risk associated with increasing exposure time; this analysis included a subgroup with >5 years of cumulative exposure (RR, 1.01; 95% CI, 0.94 to 1.08). Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. Confidence intervals were narrow, allowing exclusion of a 4% increase in the risk of cancer. Use of filled prescriptions as a measure of drug exposure eliminates recall bias and improves the precision of information on specific drugs used. Oxford University Press is a department of the University of Oxford. We aimed to detect any possible risk associated with ARB use, if present, and did not correct for multiple testing in subgroup analyses. 32 mg. eprosartan (TEVETON) 2 . We used new users of ACE inhibitors as the comparison group. were considered as the ACEi/ARB continuation group. Table 1. Patients suspending ACEis/ARBs during hospitalization for clinical reasons (e.g. RR indicates rate ratio; CI, confidence interval. Those who had filled a prescription for ARBs or ACE inhibitors during a washout period of 2 years before cohort entry were excluded. Ethics approval is not required for registry-based research in Denmark. Figure 2. The primary outcome was mortality. Drug Indications Dose Dose adjustments Comments ; ACE inhibitors: Ramipril: HF, HTN: Start: 2.5 mg oral QD Target dose: 5 mg BID: CrCl < 40ml/min: start 1.25 mg QD, max 5 mg/daycaution in elderly and hepatic impairment: Check renal … In subgroup analyses, there was a significant association between ARB use and cancer of male genital organs (rate ratio, 1.15; 95% confidence interval, 1.02 to 1.28), but no significantly increased risk of any of the other 15 cancer subgroups, including lung cancer (rate ratio, 0.92; 95% confidence interval, 0.82 to 1.02). Association between use of angiotensin receptor blockers (ARBs) and risk of incident cancer by anatomic site compared with use of angiotensin-converting enzyme (ACE) inhibitors in a nationwide cohort in Denmark, 1998 to 2006. If a patient develops an ACEI-induced cough, switch to an ARB. Those diagnosed with cancer or meeting other censoring criteria (defined below) during the lag period were disregarded from further analyses, thereby limiting the inclusion of participants with incipient cancer (the development of which might not have been affected by drug treatment during a short period of time). From a source population of 3 312 484 individuals, we excluded 117 012 with a history of cancer and 169 681 with previous ARB or ACE inhibitor use. This large nationwide cohort study found no significantly increased risk of cancer overall, in 15 different cancer subgroups, including lung cancer, or in cancer mortality among new users of ARBs compared with new users of ACE inhibitors. Strengths of our study include the use of individual-level nationwide registry data and a comprehensive pharmacoepidemiological design. RR indicates rate ratio; CI, confidence interval. These findings prompted the Food and Drug Administration and the European Medicines Agency to initiate a review of ARB safety.5,6, Because previous studies have failed to detect an increased risk of cancer associated with use of angiotensin-converting enzyme (ACE) inhibitors,7–11 results of the meta-analysis4 imply that mechanisms specific to ARBs, ie, inhibition of the angiotensin II type 1 receptor and associated unopposed stimulation of the type 2 receptor, may influence the development of cancer. We did not have data on smoking. Login. Michele M Ciulla, Switching to another antihypertensive effective drug when using ACEIs/ARBs to treat arterial hypertension during COVID-19, European Heart Journal, Volume 41, Issue 19, 14 May 2020, Page 1856, https://doi.org/10.1093/eurheartj/ehaa331. Our finding of no significant association between ARBs and cancer contrasts with that of a recently published meta-analysis of randomized trials by Sipahi et al,4 who found a modestly increased risk of new cancer among patients treated with ARBs (RR, 1.08; 95% CI, 1.01 to 1.15) compared with placebo or comparator drugs. RR indicates rate ratio; CI, confidence interval; ARB, angiotensin receptor blocker; and ACE, angiotensin-converting enzyme. Mineralocorticoid Receptor Antagonists in CKD: In Need of a Few Large Trials. In contrast, our study was able to exclude a 3% excess in lung cancer risk (RR, 0.92; 95% CI, 0.82 to 1.02), although an exploratory analysis by histological type found protective associations for small-cell carcinoma and cancer of other/unspecified histological type and an increased risk of adenocarcinoma. Our study, which analyzed individual-level data, confirms these findings in a large unselected nationwide cohort and extends them to include a specific analysis of lung cancer and other cancer subgroups. © American Heart Association, Inc. All rights reserved. ‡The χ2 test for categorical variables and t test for continuous variables. 1-800-242-8721 The frontier of very low (<30 mg/dL) LDL cholesterol, Anomalous origin of a grafted left internal mammary artery from the deep brachial artery, https://doi.org/10.1093/eurheartj/ehaa331, https://www.epicentro.iss.it/coronavirus/bollettino/Report-COVID-2019_20_marzo_eng.pdf, https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model, Receive exclusive offers and updates from Oxford Academic, Switching antihypertensive therapy in times of COVID-19: why we should wait for the evidence, Angiotensin receptor blockers and mineralocorticoid receptor antagonists therapy reaches better central haemodynamic parameters and avoid the episodes of atrial fibrillation, Comparison of medication adherence between fixed-dose combination of angiotensin receptor blockers and statin and free-combination therapy, Compliance with guideline-directed basic pharmacotherapy and late adverse events in patients with stable coronary artery disease after isolated surgical revascularization, Academic-industrial collaboration in the development of the first angiotensin receptor blocker: neprilysin inhibitor in the treatment of heart failure. In a nationwide registry-based cohort in Denmark, we evaluated the hypothesis that ARB use is associated with incident cancer in a comparison of new users of ARBs and ACE inhibitors. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. The results from the only subgroup analysis associated with increased risk, male genital cancer, must be interpreted with caution, considering the possibility of a chance finding resulting from multiple comparisons. The primary objective of this study was to evaluate BP control after switching of ARB therapy in patients … Tel: +39 02 55033592, Email: Search for other works by this author on: SARS-CoV2: should inhibitors of the renin–angiotensin system be withdrawn in patients with COVID-19? Hudson (1980) distinguished between code switching, code mixing, and borrowing in his section on the mixture of varieties. A one-size-fits-all polypill strategy for primary prevention in the era of precision medicine? between. A meta-analysis of randomized trials published in June 2010 suggested that use of angiotensin receptor blockers (ARBs) may be associated with an increased risk of cancer, lung cancer in particular. Patients were assigned as users if they had filled a minimum of 2 consecutive prescriptions for an ARB or ACE inhibitor, and follow-up was started on the day the second prescription was filled. In addition, past use of ARBs was not associated with an increased risk of cancer (adjusted RR, 1.03; 95% CI, 0.96 to 1.11) compared with past use of ACE inhibitors. Users of ARBs or ACE inhibitors who subsequently stopped treatment were recategorized to a distinct group of patients—past users—and contributed person-time to this group from the day the maximum gap time after a prescription was exceeded. In a separate group of patients treated with ARBs other than LOS (n = 82), a significant BP reduction was observed, but no change in SUA or FEUA was observed. ARB use was also associated with a significantly reduced risk of the subgroup of other cancers in our study; thus, associations pointed in different directions. The observed significant association between ARB use and male genital cancer should therefore be viewed in the context of multiple testing because it could represent a chance finding.