Chronic stable angina treatment angiotensin converting enzyme inhibitors (ACEI) and renin angiotensin aldosterone system blockers (RAAS blockers): Difference between revisions
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In comparison to other anti-hypertensive drugs, [[ACEIs]] although remain the standard drug of choice for [[hypertension]] and [[heart failure]], it has not been shown to confer overall protection against cardiovascular complications.<ref name="pmid14615107">Turnbull F, Blood Pressure Lowering Treatment Trialists' Collaboration (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14615107 Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials.] ''Lancet'' 362 (9395):1527-35. PMID: [http://pubmed.gov/14615107 14615107]</ref> <ref name="pmid12777939">Staessen JA, Wang JG, Thijs L (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12777939 Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003.] ''J Hypertens'' 21 (6):1055-76. [http://dx.doi.org/10.1097/01.hjh.0000059044.65882.db DOI:10.1097/01.hjh.0000059044.65882.db] PMID: [http://pubmed.gov/12777939 12777939]</ref> <ref name="pmid12759325">Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12759325 Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis.] ''JAMA'' 289 (19):2534-44. [http://dx.doi.org/10.1001/jama.289.19.2534 DOI:10.1001/jama.289.19.2534] PMID: [http://pubmed.gov/12759325 12759325]</ref> | In comparison to other anti-hypertensive drugs, [[ACEIs]] although remain the standard drug of choice for [[hypertension]] and [[heart failure]], it has not been shown to confer overall protection against cardiovascular complications.<ref name="pmid14615107">Turnbull F, Blood Pressure Lowering Treatment Trialists' Collaboration (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14615107 Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials.] ''Lancet'' 362 (9395):1527-35. PMID: [http://pubmed.gov/14615107 14615107]</ref> <ref name="pmid12777939">Staessen JA, Wang JG, Thijs L (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12777939 Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003.] ''J Hypertens'' 21 (6):1055-76. [http://dx.doi.org/10.1097/01.hjh.0000059044.65882.db DOI:10.1097/01.hjh.0000059044.65882.db] PMID: [http://pubmed.gov/12777939 12777939]</ref> <ref name="pmid12759325">Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12759325 Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis.] ''JAMA'' 289 (19):2534-44. [http://dx.doi.org/10.1001/jama.289.19.2534 DOI:10.1001/jama.289.19.2534] PMID: [http://pubmed.gov/12759325 12759325]</ref> | ||
==Supportive trial data== | ==Supportive trial data demonstrating significant benefit with the use of ACEIs== | ||
*In the '''HOPE trial''', 9,297 [[Chronic stable angina assessing the pretest probability of coronary artery disease|high-risk]] patients with evidence of vascular disease or [[diabetes]] plus one other cardiovascular risk factor in the absence of [[heart failure]], were randomized to receive either [[ramipril]] (10 mg/day) or placebo, to assess the role of [[ACEIs|angiotensin-converting-enzyme inhibitor]] in the management of patients with [[EF|preserved left ventricular function]] and who are at increased risk for cardiovascular events. The primary end-points from cardiovascular causes of mortality ''(6.1% in the ramipril group vs. 8.1% in the placebo group; relative risk, 0.74; P<0.001)'', [[MI|non-fatal MI]] ''(9.9% vs. 12.3%; relative risk, 0.80; P<0.001)'', [[stroke]] ''(3.4% vs. 4.9%; relative risk, 0.68; P<0.001)'' and complications related to [[diabetes]] ''(6.4% vs. 7.6%; relative risk, 0.84; P=0.03)'' was significantly reduced in the [[ramipril]] group as observed during a mean follow-up of 5 years. The 22% relative risk reduction in cardiovascular death, [[myocardial infarction]], or [[stroke]] observed with [[ramipril]] was independent of other therapies such as [[Chronic stable angina treatment aspirin|aspirin]], [[Chronic stable angina treatment beta blockers|beta-blockers]] and [[Chronic stable angina treatment anti-lipid agents|anti-lipid agents]].<ref name="pmid11479247">Dagenais GR, Yusuf S, Bourassa MG, Yi Q, Bosch J, Lonn EM et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11479247 Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study.] ''Circulation'' 104 (5):522-6. PMID: [http://pubmed.gov/11479247 11479247]</ref><ref name="pmid11909785">Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B et al. (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11909785 Use of ramipril in preventing stroke: double blind randomised trial.] ''BMJ'' 324 (7339):699-702. PMID: [http://pubmed.gov/11909785 11909785]</ref> Thus, the study was prematurely terminated after a 5-year follow-up, as [[ramipril]] was associated with a significant reduction in the mortality, [[MI]] and [[stroke]] in high-risk patients with preserved ejection fraction.<ref name="pmid10639539">Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10639539 Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.] ''N Engl J Med'' 342 (3):145-53. [http://dx.doi.org/10.1056/NEJM200001203420301 DOI:10.1056/NEJM200001203420301] PMID: [http://pubmed.gov/10639539 10639539]</ref><ref name="pmid12204499">Lonn E, Roccaforte R, Yi Q, Dagenais G, Sleight P, Bosch J et al. (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12204499 Effect of long-term therapy with ramipril in high-risk women.] ''J Am Coll Cardiol'' 40 (4):693-702. PMID: [http://pubmed.gov/12204499 12204499]</ref><ref name="pmid10675071"> (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10675071 Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators.] ''Lancet'' 355 (9200):253-9. PMID: [http://pubmed.gov/10675071 10675071]</ref> | *In the '''HOPE trial''', 9,297 [[Chronic stable angina assessing the pretest probability of coronary artery disease|high-risk]] patients with evidence of vascular disease or [[diabetes]] plus one other cardiovascular risk factor in the absence of [[heart failure]], were randomized to receive either [[ramipril]] (10 mg/day) or placebo, to assess the role of [[ACEIs|angiotensin-converting-enzyme inhibitor]] in the management of patients with [[EF|preserved left ventricular function]] and who are at increased risk for cardiovascular events. The primary end-points from cardiovascular causes of mortality ''(6.1% in the ramipril group vs. 8.1% in the placebo group; relative risk, 0.74; P<0.001)'', [[MI|non-fatal MI]] ''(9.9% vs. 12.3%; relative risk, 0.80; P<0.001)'', [[stroke]] ''(3.4% vs. 4.9%; relative risk, 0.68; P<0.001)'' and complications related to [[diabetes]] ''(6.4% vs. 7.6%; relative risk, 0.84; P=0.03)'' was significantly reduced in the [[ramipril]] group as observed during a mean follow-up of 5 years. The 22% relative risk reduction in cardiovascular death, [[myocardial infarction]], or [[stroke]] observed with [[ramipril]] was independent of other therapies such as [[Chronic stable angina treatment aspirin|aspirin]], [[Chronic stable angina treatment beta blockers|beta-blockers]] and [[Chronic stable angina treatment anti-lipid agents|anti-lipid agents]].<ref name="pmid11479247">Dagenais GR, Yusuf S, Bourassa MG, Yi Q, Bosch J, Lonn EM et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11479247 Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study.] ''Circulation'' 104 (5):522-6. PMID: [http://pubmed.gov/11479247 11479247]</ref><ref name="pmid11909785">Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B et al. (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11909785 Use of ramipril in preventing stroke: double blind randomised trial.] ''BMJ'' 324 (7339):699-702. PMID: [http://pubmed.gov/11909785 11909785]</ref> Thus, the study was prematurely terminated after a 5-year follow-up, as [[ramipril]] was associated with a significant reduction in the mortality, [[MI]] and [[stroke]] in high-risk patients with preserved ejection fraction.<ref name="pmid10639539">Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10639539 Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.] ''N Engl J Med'' 342 (3):145-53. [http://dx.doi.org/10.1056/NEJM200001203420301 DOI:10.1056/NEJM200001203420301] PMID: [http://pubmed.gov/10639539 10639539]</ref><ref name="pmid12204499">Lonn E, Roccaforte R, Yi Q, Dagenais G, Sleight P, Bosch J et al. (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12204499 Effect of long-term therapy with ramipril in high-risk women.] ''J Am Coll Cardiol'' 40 (4):693-702. PMID: [http://pubmed.gov/12204499 12204499]</ref><ref name="pmid10675071"> (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10675071 Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators.] ''Lancet'' 355 (9200):253-9. PMID: [http://pubmed.gov/10675071 10675071]</ref> | ||
:*In a sub-study, that hypothesized the benefits of [[ramipril]] use was not confined to the reduction in blood pressure alone, calculated the blood-pressure-related risk estimates from the placebo group of the HOPE trial, and from earlier studies. The study concluded that the benefits associated with [[ramipril]] were additive in patients with normal or higher than normal [[blood pressure|baseline blood pressure]].<ref name="pmid11784631">Sleight P, Yusuf S, Pogue J, Tsuyuki R, Diaz R, Probstfield J et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11784631 Blood-pressure reduction and cardiovascular risk in HOPE study.] ''Lancet'' 358 (9299):2130-1. [http://dx.doi.org/10.1016/S0140-6736(01)07186-0 DOI:10.1016/S0140-6736(01)07186-0] PMID: [http://pubmed.gov/11784631 11784631]</ref> | :*In a '''sub-study''', that hypothesized the benefits of [[ramipril]] use was not confined to the reduction in blood pressure alone, calculated the blood-pressure-related risk estimates from the placebo group of the HOPE trial, and from earlier studies. The study concluded that the benefits associated with [[ramipril]] were additive in patients with normal or higher than normal [[blood pressure|baseline blood pressure]].<ref name="pmid11784631">Sleight P, Yusuf S, Pogue J, Tsuyuki R, Diaz R, Probstfield J et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11784631 Blood-pressure reduction and cardiovascular risk in HOPE study.] ''Lancet'' 358 (9299):2130-1. [http://dx.doi.org/10.1016/S0140-6736(01)07186-0 DOI:10.1016/S0140-6736(01)07186-0] PMID: [http://pubmed.gov/11784631 11784631]</ref> | ||
:*In another substudy, that assessed the comparative effects of [[ramipril]] on [[blood pressure|ambulatory (ABP)]] and [[blood pressure|office blood pressures (OBP)]], observed that [[ramipril]] did not significantly reduce the [[blood pressure|OBP]] ''(8/2 mm Hg, P=not significant)'' or [[blood pressure|ABP]] ''(6/2 mm Hg, P=not significant)'' after 1 year. However, the 24-hour ABP was significantly reduced ''(10/4 mm Hg, P=0.03)'', as a consequent of a more pronounced blood pressure lowering effect occurring during nighttime ''(17/8 mm Hg, P<0.001)''.<ref name="pmid11751742">Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11751742 Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy.] ''Hypertension'' 38 (6):E28-32. PMID: [http://pubmed.gov/11751742 11751742]</ref> | :*In another '''substudy''', that assessed the comparative effects of [[ramipril]] on [[blood pressure|ambulatory (ABP)]] and [[blood pressure|office blood pressures (OBP)]], observed that [[ramipril]] did not significantly reduce the [[blood pressure|OBP]] ''(8/2 mm Hg, P=not significant)'' or [[blood pressure|ABP]] ''(6/2 mm Hg, P=not significant)'' after 1 year. However, the 24-hour ABP was significantly reduced ''(10/4 mm Hg, P=0.03)'', as a consequent of a more pronounced blood pressure lowering effect occurring during nighttime ''(17/8 mm Hg, P<0.001)''.<ref name="pmid11751742">Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11751742 Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy.] ''Hypertension'' 38 (6):E28-32. PMID: [http://pubmed.gov/11751742 11751742]</ref> | ||
*In the '''EUROPA trial''', 13,655 patients with previous [[myocardial infarction]] ''(64%)'', angiographic evidence of [[coronary artery disease]] ''(61%)'', [[revascularization|coronary revascularisation]] ''(55%)'', or a [[Chronic stable angina risk assessment in patients with an intermediate or high probability of coronary artery disease|positive stress test]] ''(5%)'', were randomized to receive either [[perindopril]] (8 mg/day) or placebo, to assess the effect of [[ACEI|ACE inhibition]] in the reduction of cardiovascular risk in patients with [[Chronic stable angina definition|stable coronary artery disease]] in the absence of [[heart failure]]. The study designs of both the HOPE and EUROPA trials were similar; however, the EUROPA trial involved patients with lower rates of [[hypertension]], [[diabetes]] and [[peripheral artery disease]] ''(27% in the EUROPA trial vs. 47% in the HOPE trial)''. Approximately, a 20% relative reduction in the primary endpoint of all cardiovascular causes of mortality including [[MI]] or [[cardiac arrest]] during a mean follow-up of 4.2 years was observed in the [[perindopril]] group ''(8% vs. 10%, 95% CI 9-29, p=0.0003)''. Thus, the study concluded that in patients with [[Chronic stable angina definition|stable coronary heart disease]] without apparent [[heart failure]], [[perindopril]] significantly improved outcomes.<ref name="pmid13678872">Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=13678872 Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study).] ''Lancet'' 362 (9386):782-8. PMID: [http://pubmed.gov/13678872 13678872]</ref> | *In the '''EUROPA trial''', 13,655 patients with previous [[myocardial infarction]] ''(64%)'', angiographic evidence of [[coronary artery disease]] ''(61%)'', [[revascularization|coronary revascularisation]] ''(55%)'', or a [[Chronic stable angina risk assessment in patients with an intermediate or high probability of coronary artery disease|positive stress test]] ''(5%)'', were randomized to receive either [[perindopril]] (8 mg/day) or placebo, to assess the effect of [[ACEI|ACE inhibition]] in the reduction of cardiovascular risk in patients with [[Chronic stable angina definition|stable coronary artery disease]] in the absence of [[heart failure]]. The study designs of both the HOPE and EUROPA trials were similar; however, the EUROPA trial involved patients with lower rates of [[hypertension]], [[diabetes]] and [[peripheral artery disease]] ''(27% in the EUROPA trial vs. 47% in the HOPE trial)''. Approximately, a 20% relative reduction in the primary endpoint of all cardiovascular causes of mortality including [[MI]] or [[cardiac arrest]] during a mean follow-up of 4.2 years was observed in the [[perindopril]] group ''(8% vs. 10%, 95% CI 9-29, p=0.0003)''. Thus, the study concluded that in patients with [[Chronic stable angina definition|stable coronary heart disease]] without apparent [[heart failure]], [[perindopril]] significantly improved outcomes.<ref name="pmid13678872">Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=13678872 Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study).] ''Lancet'' 362 (9386):782-8. PMID: [http://pubmed.gov/13678872 13678872]</ref> | ||
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:*The '''PERSUADE substudy''', further strengthened the benefit of [[perindopril]] in the reduction of major cardiovascular events in [[DM|diabetic]] patients with [[CAD|coronary disease]].<ref name="pmid15860521">Daly CA, Fox KM, Remme WJ, Bertrand ME, Ferrari R, Simoons ML et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15860521 The effect of perindopril on cardiovascular morbidity and mortality in patients with diabetes in the EUROPA study: results from the PERSUADE substudy.] ''Eur Heart J'' 26 (14):1369-78. [http://dx.doi.org/10.1093/eurheartj/ehi225 DOI:10.1093/eurheartj/ehi225] PMID: [http://pubmed.gov/15860521 15860521]</ref> | :*The '''PERSUADE substudy''', further strengthened the benefit of [[perindopril]] in the reduction of major cardiovascular events in [[DM|diabetic]] patients with [[CAD|coronary disease]].<ref name="pmid15860521">Daly CA, Fox KM, Remme WJ, Bertrand ME, Ferrari R, Simoons ML et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15860521 The effect of perindopril on cardiovascular morbidity and mortality in patients with diabetes in the EUROPA study: results from the PERSUADE substudy.] ''Eur Heart J'' 26 (14):1369-78. [http://dx.doi.org/10.1093/eurheartj/ehi225 DOI:10.1093/eurheartj/ehi225] PMID: [http://pubmed.gov/15860521 15860521]</ref> | ||
:*In another substudy, involving 12,056 patients with [[Chronic stable angina definition|stable coronary artery disease]] without [[heart failure]], that assessed the benefit of [[ACEIs|ACE inhibition]] in patients with mild to moderate [[renal insufficiency]] reported similar benefits of [[perindopril]] consistent with the EUROPA trial and that the effects of [[ACEIs|ACE inhibition]] were not modified by the presence of mild to moderate [[renal insufficiency]].<ref name="pmid18036453">Brugts JJ, Boersma E, Chonchol M, Deckers JW, Bertrand M, Remme WJ et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18036453 The cardioprotective effects of the angiotensin-converting enzyme inhibitor perindopril in patients with stable coronary artery disease are not modified by mild to moderate renal insufficiency: insights from the EUROPA trial.] ''J Am Coll Cardiol'' 50 (22):2148-55. [http://dx.doi.org/10.1016/j.jacc.2007.08.029 DOI:10.1016/j.jacc.2007.08.029] PMID: [http://pubmed.gov/18036453 18036453]</ref> | :*In another '''substudy''', involving 12,056 patients with [[Chronic stable angina definition|stable coronary artery disease]] without [[heart failure]], that assessed the benefit of [[ACEIs|ACE inhibition]] in patients with mild to moderate [[renal insufficiency]] reported similar benefits of [[perindopril]] consistent with the EUROPA trial and that the effects of [[ACEIs|ACE inhibition]] were not modified by the presence of mild to moderate [[renal insufficiency]].<ref name="pmid18036453">Brugts JJ, Boersma E, Chonchol M, Deckers JW, Bertrand M, Remme WJ et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18036453 The cardioprotective effects of the angiotensin-converting enzyme inhibitor perindopril in patients with stable coronary artery disease are not modified by mild to moderate renal insufficiency: insights from the EUROPA trial.] ''J Am Coll Cardiol'' 50 (22):2148-55. [http://dx.doi.org/10.1016/j.jacc.2007.08.029 DOI:10.1016/j.jacc.2007.08.029] PMID: [http://pubmed.gov/18036453 18036453]</ref> | ||
==Supportive trial data demonstrating no benefit with the use of ACEIs== | |||
*In the '''PEACE trial''', 8,290 patients with a mean baseline blood pressure 133/78, were randomized to receive either [[trandolapril]] (4mg/day) or placebo, to test the hypothesis that patients with [[Chronic stable angina definition|stable coronary artery disease]] without [[heart failure]] derive therapeutic benefit from the addition of [[ACEIs|ACE inhibitors]] to conventional therapy. The primary end point from all causes of mortality, [[MI]], [[revascularization|coronary revascularization]] during a median 4.8 year follow-up did not differ between the two groups: 21.9% in the [[trandolapril]] group and 22.5% in the placebo group (p=0.43).<ref name="pmid15531767">Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15531767 Angiotensin-converting-enzyme inhibition in stable coronary artery disease.] ''N Engl J Med'' 351 (20):2058-68. [http://dx.doi.org/10.1056/NEJMoa042739 DOI:10.1056/NEJMoa042739] PMID: [http://pubmed.gov/15531767 15531767]</ref> | |||
==ACC/AHA Guidelines- Pharmacotherapy to Prevent MI and Death and Reduce Symptoms (DO NOT EDIT) <ref name="pmid12515758">Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12515758 ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina).] ''Circulation'' 107 (1):149-58.[http://content.onlinejacc.org/cgi/reprint/41/1/159.pdf] PMID: [http://pubmed.gov/12515758 12515758]</ref> <ref name="pmid17998462">Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17998462 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.] ''Circulation'' 116 (23):2762-72.[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf] PMID: [http://pubmed.gov/17998462 17998462]</ref>== | ==ACC/AHA Guidelines- Pharmacotherapy to Prevent MI and Death and Reduce Symptoms (DO NOT EDIT) <ref name="pmid12515758">Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12515758 ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina).] ''Circulation'' 107 (1):149-58.[http://content.onlinejacc.org/cgi/reprint/41/1/159.pdf] PMID: [http://pubmed.gov/12515758 12515758]</ref> <ref name="pmid17998462">Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17998462 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.] ''Circulation'' 116 (23):2762-72.[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf] PMID: [http://pubmed.gov/17998462 17998462]</ref>== |
Revision as of 02:10, 4 September 2011
Chronic stable angina Microchapters | ||
Classification | ||
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Differentiating Chronic Stable Angina from Acute Coronary Syndromes | ||
Diagnosis | ||
Alternative Therapies for Refractory Angina | ||
Discharge Care | ||
Guidelines for Asymptomatic Patients | ||
Case Studies | ||
Chronic stable angina treatment angiotensin converting enzyme inhibitors (ACEI) and renin angiotensin aldosterone system blockers (RAAS blockers) On the Web | ||
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [6] Phone:617-632-7753; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [7]; John Fani Srour, M.D.; Jinhui Wu, M.D.; Lakshmi Gopalakrishnan, M.B.B.S.
Overview
Patients diagnosed with syndrome X and hypertension may have microvascular angina where in there is a reduced coronary vasodilator reserve and increased sympathetic drive. ACE inhibition in such patients may attenuate sympathetic coronary vasoconstriction and normalize thallium perfusion defects and reduce exercise-induced ischemia with subsequent increase in myocardial oxygen supply.[1] [2]
Mechanisms of benefit
- Based on a meta-analysis, high blood pressure was strongly and directly related to overall mortality and hence lowering blood pressure provides a greater benefit in the reduction of cardiovascular mortality and improves prognosis.[3] However, blood pressure lowering effects were found to be similar among angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and calcium channel blockers.[4] [5]
- ACE inhibition in patients with syndrome X and hypertension, may attenuate sympathetic coronary vasoconstriction and reduce exercise-induced ischemia with subsequent increase in myocardial oxygen supply.[1] [2]
- In diabetics with post-MI, ACE inhibition may slow the rate of progression of proteinuric chronic renal failure.[6] [7]
Indications
- In patients with coronary artery disease and preserved left ventricular function, ACEIs may be indicated for secondary preventive therapy.[8] [9] [10]
- ACEIs or ARBs has shown to prevent the progression of renal dysfunction and hence are used as the first-line of agents in the management of hypertension in diabetics with microalbuminuria.[6] [7]
Adverse effects
In comparison to other anti-hypertensive drugs, ACEIs although remain the standard drug of choice for hypertension and heart failure, it has not been shown to confer overall protection against cardiovascular complications.[4] [5] [11]
Supportive trial data demonstrating significant benefit with the use of ACEIs
- In the HOPE trial, 9,297 high-risk patients with evidence of vascular disease or diabetes plus one other cardiovascular risk factor in the absence of heart failure, were randomized to receive either ramipril (10 mg/day) or placebo, to assess the role of angiotensin-converting-enzyme inhibitor in the management of patients with preserved left ventricular function and who are at increased risk for cardiovascular events. The primary end-points from cardiovascular causes of mortality (6.1% in the ramipril group vs. 8.1% in the placebo group; relative risk, 0.74; P<0.001), non-fatal MI (9.9% vs. 12.3%; relative risk, 0.80; P<0.001), stroke (3.4% vs. 4.9%; relative risk, 0.68; P<0.001) and complications related to diabetes (6.4% vs. 7.6%; relative risk, 0.84; P=0.03) was significantly reduced in the ramipril group as observed during a mean follow-up of 5 years. The 22% relative risk reduction in cardiovascular death, myocardial infarction, or stroke observed with ramipril was independent of other therapies such as aspirin, beta-blockers and anti-lipid agents.[12][13] Thus, the study was prematurely terminated after a 5-year follow-up, as ramipril was associated with a significant reduction in the mortality, MI and stroke in high-risk patients with preserved ejection fraction.[9][14][15]
- In a sub-study, that hypothesized the benefits of ramipril use was not confined to the reduction in blood pressure alone, calculated the blood-pressure-related risk estimates from the placebo group of the HOPE trial, and from earlier studies. The study concluded that the benefits associated with ramipril were additive in patients with normal or higher than normal baseline blood pressure.[16]
- In another substudy, that assessed the comparative effects of ramipril on ambulatory (ABP) and office blood pressures (OBP), observed that ramipril did not significantly reduce the OBP (8/2 mm Hg, P=not significant) or ABP (6/2 mm Hg, P=not significant) after 1 year. However, the 24-hour ABP was significantly reduced (10/4 mm Hg, P=0.03), as a consequent of a more pronounced blood pressure lowering effect occurring during nighttime (17/8 mm Hg, P<0.001).[17]
- In the EUROPA trial, 13,655 patients with previous myocardial infarction (64%), angiographic evidence of coronary artery disease (61%), coronary revascularisation (55%), or a positive stress test (5%), were randomized to receive either perindopril (8 mg/day) or placebo, to assess the effect of ACE inhibition in the reduction of cardiovascular risk in patients with stable coronary artery disease in the absence of heart failure. The study designs of both the HOPE and EUROPA trials were similar; however, the EUROPA trial involved patients with lower rates of hypertension, diabetes and peripheral artery disease (27% in the EUROPA trial vs. 47% in the HOPE trial). Approximately, a 20% relative reduction in the primary endpoint of all cardiovascular causes of mortality including MI or cardiac arrest during a mean follow-up of 4.2 years was observed in the perindopril group (8% vs. 10%, 95% CI 9-29, p=0.0003). Thus, the study concluded that in patients with stable coronary heart disease without apparent heart failure, perindopril significantly improved outcomes.[10]
- The PERSUADE substudy, further strengthened the benefit of perindopril in the reduction of major cardiovascular events in diabetic patients with coronary disease.[18]
- In another substudy, involving 12,056 patients with stable coronary artery disease without heart failure, that assessed the benefit of ACE inhibition in patients with mild to moderate renal insufficiency reported similar benefits of perindopril consistent with the EUROPA trial and that the effects of ACE inhibition were not modified by the presence of mild to moderate renal insufficiency.[19]
Supportive trial data demonstrating no benefit with the use of ACEIs
- In the PEACE trial, 8,290 patients with a mean baseline blood pressure 133/78, were randomized to receive either trandolapril (4mg/day) or placebo, to test the hypothesis that patients with stable coronary artery disease without heart failure derive therapeutic benefit from the addition of ACE inhibitors to conventional therapy. The primary end point from all causes of mortality, MI, coronary revascularization during a median 4.8 year follow-up did not differ between the two groups: 21.9% in the trandolapril group and 22.5% in the placebo group (p=0.43).[8]
ACC/AHA Guidelines- Pharmacotherapy to Prevent MI and Death and Reduce Symptoms (DO NOT EDIT) [20] [21]
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Class I1. ACE inhibitors in all patients with significant coronary artery disease by angiography or previous myocardial infarction who also have diabetes and/or left ventricular systolic dysfunction. (Level of Evidence: A) 2. ACE inhibitors should be started and continued indefinitely in all patients with left ventricular ejection fraction less than or equal to 40% and in those with hypertension, diabetes, or chronic kidney disease unless contraindicated. (Level of Evidence: A) 3. ACE inhibitors should be started and continued indefinitely in patients who are not lower risk (lower risk defined as those with normal left ventricular ejection fraction in whom cardiovascular risk factors are well controlled and revascularization has been performed), unless contraindicated. (Level of Evidence: B) 4. Angiotensin receptor blockers are recommended for patients who have hypertension, have indications for but are intolerant of ACE inhibitors, have heart failure, or have had a myocardial infarction with left ventricular ejection fraction less than or equal to 40%. (Level of Evidence: A) 5. Aldosterone blockade is recommended for use in post-MI patients without significant renal dysfunction (creatinine should be less than 2.5 mg per dL in men and less than 2.0 mg per dL in women) or hyperkalemia (potassium should be less than 5.0 mEq per L) who are already receiving therapeutic doses of an ACE inhibitor and a beta blocker, have a left ventricular ejection fraction less than or equal to 40%, and have either diabetes or heart failure. (Level of Evidence: A) Class IIa1. ACE inhibitor in patients with coronary artery disease by angiography or previous myocardial infarction or other vascular disease. (Level of Evidence: B) 2. It is reasonable to use ACE inhibitors among lower-risk patients with mildly reduced or normal left ventricular ejection fraction in whom cardiovascular risk factors are well controlled and revascularization has been performed. (Level of Evidence: B) Class IIb1. Angiotensin receptor blockers may be considered in combination with ACE inhibitors for heart failure due to left ventricular systolic dysfunction. (Level of Evidence: B) |
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ESC Guidelines- Pharmacological therapy to improve prognosis in patients with stable angina (DO NOT EDIT) [22]
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Class I1. ACE-inhibitor therapy in patients with coincident indications for ACE-inhibition, such as hypertension, heart failure, LV dysfunction, prior MI with LV dysfunction, or diabetes. (Level of Evidence: A) Class IIa1. ACE-inhibitor therapy in all patients with angina and proven coronary disease. (Level of Evidence: B) |
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Vote on and Suggest Revisions to the Current Guidelines
Sources
- TheACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina [20]
- The 2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina [21]
- Guidelines on the management of stable angina pectoris: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology [22]
- The ACC/AHA/ACP–ASIM Guidelines for the Management of Patients With Chronic Stable Angina [23]
References
- ↑ 1.0 1.1 Kaski JC, Rosano G, Gavrielides S, Chen L (1994) Effects of angiotensin-converting enzyme inhibition on exercise-induced angina and ST segment depression in patients with microvascular angina. J Am Coll Cardiol 23 (3):652-7. PMID: 8113548
- ↑ 2.0 2.1 van den Heuvel AF, Dunselman PH, Kingma T, Verhorst P, Boomsma F, van Gilst WH et al. (2001) Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade. J Am Coll Cardiol 37 (2):470-4. PMID: 11216965
- ↑ Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360 (9349):1903-13. PMID: 12493255
- ↑ 4.0 4.1 Turnbull F, Blood Pressure Lowering Treatment Trialists' Collaboration (2003) Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 362 (9395):1527-35. PMID: 14615107
- ↑ 5.0 5.1 Staessen JA, Wang JG, Thijs L (2003) Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003. J Hypertens 21 (6):1055-76. DOI:10.1097/01.hjh.0000059044.65882.db PMID: 12777939
- ↑ 6.0 6.1 European Society of Hypertension-European Society of Cardiology Guidelines Committee (2003)2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 21 (6):1011-53.DOI:10.1097/01.hjh.0000059051.65882.32PMID: 12777938
- ↑ 7.0 7.1 American Diabetes Association (2003) Standards of medical care for patients with diabetes mellitus. Diabetes Care 26 Suppl 1 ():S33-50. PMID: [1]
- ↑ 8.0 8.1 Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J et al. (2004) Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 351 (20):2058-68. DOI:10.1056/NEJMoa042739 PMID: 15531767
- ↑ 9.0 9.1 Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342 (3):145-53. DOI:10.1056/NEJM200001203420301 PMID: 10639539
- ↑ 10.0 10.1 Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators (2003) Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 362 (9386):782-8. PMID: 13678872
- ↑ Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH et al. (2003) Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA 289 (19):2534-44. DOI:10.1001/jama.289.19.2534 PMID: 12759325
- ↑ Dagenais GR, Yusuf S, Bourassa MG, Yi Q, Bosch J, Lonn EM et al. (2001) Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study. Circulation 104 (5):522-6. PMID: 11479247
- ↑ Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B et al. (2002) Use of ramipril in preventing stroke: double blind randomised trial. BMJ 324 (7339):699-702. PMID: 11909785
- ↑ Lonn E, Roccaforte R, Yi Q, Dagenais G, Sleight P, Bosch J et al. (2002) Effect of long-term therapy with ramipril in high-risk women. J Am Coll Cardiol 40 (4):693-702. PMID: 12204499
- ↑ (2000) Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 355 (9200):253-9. PMID: 10675071
- ↑ Sleight P, Yusuf S, Pogue J, Tsuyuki R, Diaz R, Probstfield J et al. (2001) Blood-pressure reduction and cardiovascular risk in HOPE study. Lancet 358 (9299):2130-1. DOI:10.1016/S0140-6736(01)07186-0 PMID: 11784631
- ↑ Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J (2001) Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy. Hypertension 38 (6):E28-32. PMID: 11751742
- ↑ Daly CA, Fox KM, Remme WJ, Bertrand ME, Ferrari R, Simoons ML et al. (2005) The effect of perindopril on cardiovascular morbidity and mortality in patients with diabetes in the EUROPA study: results from the PERSUADE substudy. Eur Heart J 26 (14):1369-78. DOI:10.1093/eurheartj/ehi225 PMID: 15860521
- ↑ Brugts JJ, Boersma E, Chonchol M, Deckers JW, Bertrand M, Remme WJ et al. (2007) The cardioprotective effects of the angiotensin-converting enzyme inhibitor perindopril in patients with stable coronary artery disease are not modified by mild to moderate renal insufficiency: insights from the EUROPA trial. J Am Coll Cardiol 50 (22):2148-55. DOI:10.1016/j.jacc.2007.08.029 PMID: 18036453
- ↑ 20.0 20.1 Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). Circulation 107 (1):149-58.[2] PMID: 12515758
- ↑ 21.0 21.1 Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina. Circulation 116 (23):2762-72.[3] PMID: 17998462
- ↑ 22.0 22.1 Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F; et al. (2006). [url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367 [4] "Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology"] Check
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value (help). Eur Heart J. 27 (11): 1341–81. doi:10.1093/eurheartj/ehl001. PMID 16735367. - ↑ Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM et al. (1999) ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: executive summary and recommendations. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina). Circulation 99 (21):2829-48. [5] PMID: 10351980