* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Suggestion from clinicians
Neuropharmacology wikipedia , lookup
Adherence (medicine) wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Psychopharmacology wikipedia , lookup
MTOR inhibitors wikipedia , lookup
Discovery and development of dipeptidyl peptidase-4 inhibitors wikipedia , lookup
Discovery and development of HIV-protease inhibitors wikipedia , lookup
Drug interaction wikipedia , lookup
Discovery and development of direct thrombin inhibitors wikipedia , lookup
Discovery and development of cyclooxygenase 2 inhibitors wikipedia , lookup
Discovery and development of direct Xa inhibitors wikipedia , lookup
Discovery and development of integrase inhibitors wikipedia , lookup
Theralizumab wikipedia , lookup
Discovery and development of neuraminidase inhibitors wikipedia , lookup
Metalloprotease inhibitor wikipedia , lookup
Discovery and development of ACE inhibitors wikipedia , lookup
Enalapril vs. Ramipril vs. Other ACEi Replacement to the List Peer Feedback: “ramipril (better mortality in CHF, See Pilote et all CMAJ 2008), dosing in study table of enalipril is incorrect - it is BID not OD. Same cost” “lisinopril/ramipril - enalapril is BID drug for heart failure and frequently for HTN" “Comment: Add ace-inhibitors: perindopril, Lisinopril, ramipril, trandilopril” "Comment: Other notes- hypertension is one of the most common problems for all physicians. You do not have diltiazem CD or other ACEi on your list (lisinopril, rampril, perindopril). Perindopril and ramipril are the cheapest, both long acting and both with fantastic supporting RCT evidence." Literature Review Question: Does Ramipril have better efficacy then enalipril? What is the most effective ACE inhibitor? Literature Search: Include article cited by peer reviewer Cochrane Review CADTH Pubmed: “ramipril AND enalapril AND efficacy AND comparison”; “(angiotensin-converting enzyme inhibitors OR ace inhibitors) AND (efficacy OR safety OR mortality) AND (enalapril OR ramipril OR perindopril OR lisinopril OR trandolapril) AND (hypertension OR heart failure)” eCPS - Cardiovascular Disorders: Heart Failure, Cardiovascular Disorders: Hypertension Different ACEi and Mortality (2015) A total of 989,489 ACE inhibitors initiators were included in the analysis. The results of this study showed that among ACE initiators, captopril was associated with an increased risk, while enalapril and fosinopril were associated with a significant but lesser increased risk of death as compared with ramipril. The increased risk associated with these three ACE inhibitors was consistently observed across a range of subgroups of hypertensive patients with or without a variety of complications. Perindopril, lisinopril, and imidapril had similar mortality risk as ramipril. ACE inhibitors may differ with respect to reducing mortality for patients with hypertension. Among all ACE inhibitors, ramipril and perindopril were the most comprehensively evaluated agents in patients with a variety of underlying conditions.17–24 Although generally being beneficial, the results of ACE inhibitor trials regarding trandolapril, quinapril, and lisinopril have not always been consistent.25–28 No large randomized controlled trial evaluating the long-term outcome has been reported for imidapril. The beneficial effects of enalapril and fosinopril were inconsistent across trials.30–32 The present study again suggests that the mortality risk profile for ramipril is better than enalapril and fosinopril in patients with hypertension. Besides, the increased cancer mortality risk associated with fosinopril should be interpreted with caution because the follow-up of the current study might not be long enough to identify the small differences in cancer death.33 In summary, enalapril and fosinopril were associated with a modestly increased risk compared to lisinopril, perindopril, ramipril, and imidapril. However, the differences in mortality risk among individual ACE inhibitors were only marginal and might be of limited clinical significance. On the other hand, despite that uncontrolled confounding might still exist, there was a consistent increased mortality risk associated with captopril use. It might be reasonable to avoid long-term captopril use in hypertensive patients if there was no other evidence-supported indication. The current study suggests that there are modest differences in overall and cause-specific mortality risk among individual ACE inhibitors, although the observed association might be due to residual confounding effect. The clinical significance of these findings should be further evaluated and clarified. Chang, Chia-Hsuin, et al. "Different angiotensin-converting enzyme inhibitors and the associations with overall and cause-specific mortalities in patients with hypertension." American journal of hypertension 28.6 (2015): 823-830. CADTH (2015) Patients with diabetes mellitus type II While both imidapril and ramipril significantly reduced blood pressure, UAE, and BNP in patients with DM, HTN, and microalbuminurea, the reduction of UAE was statistically significantly more profound with imidapril than ramipril starting from the sixth week and onwards.11 The addition of bendoflumethiazide to captopril in patients with HTN and DM led to better control of BP when compared with captopril alone. However, this combination also led to deterioration in fasting blood glucose level.12 Patients with heart failure One systematic review identified three trials that compared perindopril to enalapril. Authors of the review reported greater effectiveness of enalapril for improving cardiac sympathetic nerve activity, NYHA functional class, and BNP.13 Patients with hypertension Pretax (perindopril and indapamide) was shown, in two double blind RCTs, to be more effective in reducing diastolic BP than cilazapril monotherapy.14,16 However, the combination also led to a reduction in the benefits obtained from statin therapy on patients’ metabolic profile.14 ACE inhibitors that contained a phosphonate group (namely fosinopril) were associated with more coughing and hypotension than ACE inhibitors that contained di-carboxyl group (namely enalapril, lisinopril, and ramipril). While the di-carboxyl group containing ACE inhibitors were associated with more cases of nausea than the phosphate containing ACE inhibitor.15 Patients with myocardial infarction In patients with left ventricular dysfunction after acute MI, zonfenopril significantly decreased cardiac hospitalization when compared to ramipril.17 This reduction in hospitalization led to zonfenopril being more cost-effective when compared to ramipril.18 In 2008, a previous report published by CADTH7 on the topic of comparative effectiveness of ACE inhibitors concluded that there is “limited evidence that not all ACE inhibitors are equally efficacious for various outcomes including blood pressure control, and mortality rates post MI”. New evidence identified since 2008 reinforces the previous conclusion, suggesting that imidapril might be better than ramipril in reducing urinary albumin excretion in diabetic patients with HTN, 11 and that zofenopril could be clinically better than ramipril for reducing the number of hospitalizations in post-acute MI patients, and more cost-effective. 17 Zofenopril, however, is not currently available in Canada. Evidence over other outcomes remains largely scarce with major limitations in methodology. CADTH; Angiotensin-Converting Enzyme (ACE) Inhibitors: A Review of the Comparative Clinical and Cost-Effectiveness; 12 June 2015 CADTH (2008) The purpose of this report was to provide information regarding the comparative effectiveness and safety profiles of different ACE inhibitors. Placebo-controlled randomized controlled trials (RCTs) and head-to-head RCTs were included in the assessment of effectiveness, and RCTs or large, good-quality observational studies were included in the assessment of harms. Included interventions were treatment with benazepril, captopril, cilazapril, enalapril, fosinopril, lisinopril, moexipril, quinapril, ramipril, perindopril, or trandolapril. Outcomes varied according to the clinical indication. A number of studies were identified that compared different ACE inhibitors for the treatment of patients with hypertension, recent myocardial infarction, and congestive heart failure. However, studies comparing the effectiveness of different ACE inhibitors for kidney protection were lacking. Although there is limited evidence that not all ACE inhibitors are equally efficacious for various outcomes including blood pressure control, and mortality rates post MI,16,17,36 the majority of the available trials suggest that there is no clear advantage of using one ACE inhibitor over another. Until more conclusive evidence is available, formulary decisions should also take clinical experience and acquisition costs into consideration. CADTH; Angiotensin-Converting Enzyme (ACE) inhibitors: A Comparative Effectiveness Review; 08 April 2008 Pilote et al. CMAJ 2008 Patient population: Elderly patients with congestive heart failure who filled a prescription for an ACE inhibitor within 30 days after discharge from hospital. First admission was for congestive heart failure. Our study shows that, at currently prescribed doses, enalapril and captopril were associated with about 10%–15% higher mortality than ramipril among elderly patients with congestive heart failure. Patients who filled prescriptions for fosinopril, lisinopril, quinapril, perindopril and cilazapril did not have a significantly different mortality than those who filled prescriptions for Ramipril. In summary, our results suggest that physicians choosing an ACE inhibitor for patients with congestive heart failure should consider the possible 10%–15% increase in mortality that we observed with enalapril and captopril use compared with ramipril use. Further evidence is required to fully assess the comparability between ramipril and all newer ACE inhibitors. Pilote, L., Abrahamowicz, M., Eisenberg, M., Humphries, K., Behlouli, H., & Tu, J. V. (2008). Effect of different angiotensin-converting-enzyme inhibitors on mortality among elderly patients with congestive heart failure. Canadian Medical Association Journal, 178(10), 1303-1311. Cochrane Review 2007 This review provides a reasonable amount of data to assess the trough BP lowering effect of 14 different ACE inhibitors. When the different ACE inhibitors are compared, there is a remarkable similarity in their BP lowering effects at trough. When the best estimate of the BP lowering efficacy of these 14 drugs is compared, they range from -6/-4 mm Hg to -9/-5 mm Hg. The data are most consistent with the near maximum BP lowering effect of the each of the drugs being the same. However, for most of the drugs there are insufficient data over a broad dose range. It is therefore impossible with this analysis to be certain that there are no blood pressure lowering differences between one or more of the drugs. It would require headto-head trials of different ACE inhibitors at equivalent BP lowering doses to assess whether or not there are differences between different drugs. This review will provide useful information for estimating equivalent doses and thereby designing trials to compare different ACE inhibitors. However, at the present time given that all the drugs are working by the same mechanism and the similarities in the blood pressure lowering effect it is most likely that the near maximal BP lowering of the different ACE inhibitors is the same. Conclusions 1. The review provides data on the dose-related blood pressure lowering efficacy of 14 different ACE inhibitors at trough. The best estimate of the blood pressure lowering efficacy of these 14 drugs ranges from -6/-4 to -9/-5 mm Hg. The data do not suggest that any one ACE inhibitor is better or worse at lowering blood pressure when used at doses of one-half the manufacturer’s maximal recommended dose and above. 2. A dose-response relationship for the blood pressure lowering effect of the ACE inhibitors was evident. A dose of 1/16 of the maximum recommended dose had no measurable blood pressure lowering effect. A dose of 1/8 or 1/4 of the maximum recommended daily achieved a blood pressure lowering effect that was 60 to 70% of the blood pressure lowering effect of the maximum recommended dose. A dose of 1/2 3. 4. 5. 6. 7. 8. of the maximum recommended dose achieved a blood pressure lowering effect that was 90% of the maximum recommended dose. ACE inhibitor doses above the maximum recommended dose did not significantly lower blood pressure more than the maximum recommended dose. Combining the effects of half maximum recommended doses and higher gives an estimate of the average trough blood pressure lowering efficacy for ACE inhibitors as a class of drugs of -8 mm Hg for SBP and -5 mm Hg for DBP. ACE inhibitors reduced blood pressure measured 1 to 12 hours after the dose by about 11/6 mm Hg. ACE inhibitors reduced trough pulse pressure by about 3 mm Hg. ACE inhibitors did not significantly affect resting blood pressure variability or heart rate. All doses of ACE inhibitors, whether analyzed individually or combined, did not change WDAE as compared to placebo; however, this outcome was not reported for about half the trials so there is judged to be a high risk of selective reporting bias. Heran, Balraj S., et al. "Blood pressure lowering efficacy of angiotensin converting enzyme (ACE) inhibitors for primary hypertension." The Cochrane Library (2008). eCPS (2015) Heart Failure ACE inhibitors are recommended in all patients because they improve symptoms and reduce the risk of hospitalization, MI and death in patients with systolic HF. 9,10,11 Start with a low dose and titrate at 7- to 14-day intervals to the target dose, or maximum tolerated dose if the target dose cannot be reached. Treatment with target doses is more effective than low doses. 12 Measure serum creatinine, potassium and blood pressure before initiating an ACE inhibitor or increasing the dose and 7–14 days after any increase in dosage.5 An increase in serum creatinine of up to 30% is expected and acceptable after initiation of an ACE inhibitor.1 If the increase in serum creatinine is greater than 30%, other causes of worsening renal function should first be excluded. In particular, assess volume status, as an increase in serum creatinine often appears in patients who are hypovolemic because of excessive diuresis. If no other cause for the worsening renal function can be identified, reduce the dose or discontinue the ACE inhibitor. Although data are limited, the authors recommend periodically reassessing the potential of restarting ACE inhibitors or increasing the dose if the patient's condition improves. Patients at greatest risk of hyperkalemia are those with moderate to severe renal dysfunction, high baseline potassium, diabetes mellitus and those receiving potassium-sparing diuretics.13 Drug Dosage Adverse Effects Drug Interactions Comments Costa ACE Inhibitorsb captopril generics Initial:6.25–12.5 mg TID po Target: 50 mg TID enalapril Vasotec, generics Initial: 1.25–2.5 mg BID po Target: 10 mg BID ACE Inhibitorsb lisinopril Prinivil, Zestril, generics Initial: 2.5–5 mg once daily po Target: 20–35 mg once daily ACE Inhibitorsb ramipril Initial: 1.25–2.5 mg BID po Altace, generics Target: 5 mg BID Diuretics: hypotension (monitor BP). Potassium-sparing diuretics, potassium supplements, ARBs: hyperkalemia (monitor K+). NSAIDs: reduced hypotensive effect (monitor BP), fluid retention, renal failure. Monitor serum creatinine and potassium 7–14 days after initiation of therapy or dose changes. Some experienced clinicians use doses higher than usual target doses. Avoid in pregnancy. $$$ ACE Inhibitorsb Hypotension, hyperkalemia, dry cough, renal insufficiency, angioedema (rare), skin rashes, taste disturbance, proteinuria, neutropenia (rare), headache, dizziness. ACE Inhibitorsb trandolapril Mavik Class Legend: $ < $25 Lithium: lithium toxicity (monitor lithium levels). Initial: 1 mg once daily po Target: 4 mg once daily $$ 25–50 $$$ 50–75 $$$$ 75–100 $$$$$100–125 Cardiovascular Disorders: Heart Failure; Simon de Denus, B. Pharm, MSc, PhD and Michel White, MD, FRCPC, FACC, FESC; Date of revision: May 2015 Hypertension $ $ $ $$ Angiotensin-converting enzyme (ACE) inhibitors are first-line agents for non-black patients with uncomplicated hypertension and for patients with diabetes, ischemic heart disease, recent MI, heart failure or chronic kidney disease. Drug Dosage Adverse Effects Drug Interactions Comments Costa ACE Inhibitors benazepril Lotensin, generics Initial: 10 mg/day Usual: 20 mg/day Maximum: 40 mg/day Once daily or divided BID po captopril generics Initial: 25 mg/day Usual: 75 mg/day Maximum:150 mg/day Divided BID or TID po ACE Inhibitors cilazapril Inhibace, generics Initial: 2.5 mg/day Usual: 2.5–5 mg/day Maximum: 10 mg/day Once daily or divided BID po Marked increase in serum K+ in patients receiving K+supplements and/or K+-sparing diuretics. Reduced hypotensive effect with NSAIDs and increased risk of renal dysfunction. Contraindicated in pregnancy—caution when prescribing to women of child-bearing potential.5,6 Use lower (50%) initial doses if on diuretics (increased risk of hypotension with hypovolemia). Hyperkalemia usually occurs only in those on K+supplements or drugs that cause K+ retention, those with renal impairment or diabetics with high serum K+ levels. Assess SCr and K+after a few days, then regularly. $$ ACE Inhibitors Dry cough, hyperkalemia. Unusual: angioedema. Can precipitate renal failure in renovascular disease, volume depletion or those receiving NSAIDs. Class Elevated Li+ levels (potential toxicity). $$ $ ACE Inhibitors enalapril Vasotec, generics Initial: 5 mg/day Usual: 10–40 mg/day Maximum: 40 mg/day Once daily or divided BID po ACE Inhibitors fosinopril generics Initial: 10 mg/day Usual: 20 mg/day Maximum: 40 mg/day Once daily or divided BID po ACE Inhibitors lisinopril Initial: 10 mg/day Prinivil, Zestril, generics Usual: 20 mg/day Maximum: 40 mg/day Once daily po $ ACE Inhibitors perindopril Coversyl, generics Initial: 4 mg/day Maximum: 8 mg/day Once daily or divided BID po $$ ACE Inhibitors quinapril Accupril, generics Initial: 10 mg/day Maximum: 40 mg/day Once daily or divided BID po $$ ACE Inhibitors ramipril Altace, generics Initial: 2.5 mg/day Usual: 10 mg/day Maximum: 20 mg/day Once daily or divided BID po $ ACE Inhibitors trandolapril Mavik Initial: 1 mg/day Maximum: 4 mg/day Once daily po $$ Legend: 60–80 $<20 $-$$ <20–40 $ $ $$ 20–40 $$$ 40–60 $$$$ Cardiovascular Disorders: Hypertension; Norm R.C. R. C. Campbell, MD, FRCPC, Paul Gibson, MD, FRCPC, and Ross T. Tsuyuki, PharmD, MSc, FCSHP, FACC; Date of Revision: March 2015 Medication Enalapril Uses hypertension, left ventricular dysfunction, heart failure Contraindications (CI), drug interactions (DI) or cautions CI: renal dysfunction, angioedema, pregnancy (T1, T2, T3) DI: diuretic (potassium sparing), lithium Adverse Effects (common and severe) hypotension, dizziness, headache, chest pain, cough, rash, hyperkalemia, nausea , vomiting Initial dose; typical dose 5mg; 10-40mg one time a day or divided dose BID Per RxTx app (CPS) Monitoring renal dysfunction: SCr, blood urea nitrogen (BUN), electrolytes