Dear editor
In a recent review in Vascular Health and Risk Management Wang et al state that “In mainly placebo-controlled cardiovascular (CV)-outcome studies in patients with hypertension, CV benefits with perindopril were associated with large reductions in BP.”1 However, perindopril in the European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease (EUROPA) study significantly reduced major cardiovascular events despite a small reduction (approximately 4 mmHg) in systolic blood pressure from baseline.2,3 Additionally, the average baseline blood pressure in the EUROPA was just 137/82 mmHg, and in those without hypertension, perindopril still provided a 20% reduction in the combined endpoint of cardiovascular death, myocardial infarction, and cardiac arrest.4,5 In fact, patients receiving perindopril with a baseline systolic blood pressure of <120 mmHg had the greatest reduction in the primary event.6
PERindopril–Thrombosis, InflammatioN, Endothelial dysfunction and Neurohormonal activation Trial (PERTINENT), a sub study of EUROPA, also showed that perindopril improves endothelial function, which the authors concluded may have provided the benefit and not blood pressure reduction per se.7 Thus, the notion that perindopril is only effective in hypertensive patients, and only when large reductions in blood pressure occur, is not supported by the literature.
The authors go on to state that,
The beyond-BP-lowering CV-protective benefits of telmisartan were demonstrated in the active-controlled ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) trial.
However, ambulatory and night-time systolic blood pressure was significantly lower with telmisartan versus ramipril (−3.1 mmHg and −4.1 mmHg, respectively).8 Despite this fact, telmisartan was not superior to ramipril in reducing cardiovascular events or mortality. It is also surprising that telmisartan did not significantly reduce stroke compared to ramipril, especially considering that this endpoint is strictly dependent on blood pressure reduction. For instance, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), with only a 2.7 mmHg difference, perindopril/amlodipine significantly reduced all-cause mortality (−11%) and stroke (−23%), supporting the beyond-blood pressure-lowering benefits of this particular combination (Table 1).9 Additionally, in ONTARGET, ramipril was dosed in the morning, which resulted in a clear reduction in morning blood pressure, and during the first 6 hours of the dosing interval, in favor of telmisartan.8 It was well known from the prospective, randomized investigation of the safety and efficacy of telmisartan versus ramipril using ambulatory blood pressure monitoring (PRISMA)-I and -II trials, before the onset of ONTARGET, that telmisartan provides significantly greater blood pressure reductions versus ramipril, particularly during the last 6 hours of the dosing interval, yet ramipril was dosed once a day, in the morning.10 Thus, we are left to wonder whether this was strategic, especially when previous large cardiovascular outcomes trials testing ramipril such as the Heart Outcomes Prevention Evaluation (HOPE) trial gave ramipril once daily at night and Acute Infarction Ramipril Efficacy (AIRE) gave ramipril twice daily.11,12 The most likely reason for this was to cover the early morning blood pressure surge and the loss of ramipril’s antihypertensive effect during the end of the dosing interval. Thus, ONTARGET did not dose ramipril optimally, which may have lessened any potential advantages of ramipril in the setting.
Table 1.
Trial | Treatment | Comparator | Baseline SBP | SBP difference between arms | Total mortality benefit | CI |
---|---|---|---|---|---|---|
Perindopril | ||||||
ADVANCE | Perindopril (+ indapamide) | Placebo | 145 mmHg | −5.6 mmHg | −14% | (−25; −2) |
ASCOT | Perindopril (+ amlodipine) | Atenolol + thiazide | 164 mmHg | −2.7 mmHg | −11% | (−9; −1) |
EUROPA | Perindopril | Placebo | 137 mmHg | −5 mmHg | −11% | (−22; +2) |
Telmisartan | ||||||
ONTARGET | Telmisartan (+ ramipril) | Ramipril | 142 mmHg | −2.4 mmHg | +7% | (−2; +16) |
PROFESS | Telmisartan | Placebo | 144 mmHg | −4 mmHg | +3% | (−7; +14) |
TRANSCEND | Telmisartan | Placebo | 141 mmHg | −4 mmHg | +5% | (−9; +22) |
Abbreviations: ASCOT, Anglo-Scandinavian Cardiac Outcomes Trial; EUROPA, European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease; ONTARGET, ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial; PROFESS, Prevention Regimen for Effectively Avoiding Second Strokes; TRANSCEND, Telmisartan Randomized Assessment Study in ACE intolerant; CI, confidence interval; SBP, systolic blood pressure.
With respect to blood pressure-independent benefits of telmisartan, in Telmisartan Randomized Assessment Study in ACE intolerant (TRANSCEND), telmisartan as compared to placebo in patients with cardiovascular disease, or high-risk diabetes and without heart failure, who were intolerant to angiotensin-converting enzyme inhibitors (ACE-Is), did not reduce cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure, despite a significant reduction in blood pressure.13 Additionally, in patients soon after an ischemic stroke, telmisartan (continued for 2.5 years) did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes, despite a significant reduction in blood pressure.14 Lastly, telmisartan was compared over a period of 4 years to the diuretic amiloride, with each of the two agents being combined with amlodipine. Despite similar reductions in blood pressure, telmisartan was not better than amiloride on any single cardiovascular endpoint or mortality.15 The aforementioned data do not support the notion that “telmisartan provides beyond-blood pressure-lowering benefits.” However, perindopril was found to have beyond-blood pressure-lowering benefits in the Diabetes Artery Perindopril Hypertension Normalization Excess sTiffness (DAPHNET) study.16 This trial, testing perindopril in hypertensive patients with type 2 diabetes, showed that perindopril 8 mg, as opposed to 4 mg, significantly improves carotid distensibility, despite similar reductions in ambulatory blood pressure.16 The Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) also showed that ACE-inhibitors, but not angiotensin receptor blockers (ARBs), have blood-pressure-independent effects on the risk of major coronary disease events.17 Additionally, a meta-regression by the BPLTTC also showed risk reductions of 28% in stroke, 22% in major cardiovascular events, 20% in cardiovascular death, 20% in coronary heart disease, 18% in heart failure, and 12% in all-cause mortality with ACE-Is versus placebo.18 These data provide strong evidence that ACE-Is, particularly perindopril, provides cardiovascular protection beyond blood pressure lowering.
Another point that we take issue with is,
ACE inhibitors and ARBs have been shown in head-to-head comparison trials to have comparable CV protective effects.
In Diabetics Exposed to Telmisartan and Enalapril (DETAIL), telmisartan (80 mg daily) was directly compared to enalapril (20 mg daily) in a randomized, multicenter, double-blind, 5 year study.19 This trial was composed of 250 subjects with type 2 diabetes and early nephropathy. Despite a larger reduction in systolic blood pressure with telmisartan (−6.9 mmHg) as compared to enalapril (−2.9 mmHg), there was a less marked deterioration in the glomerular filtration rate, although not statistically so, with enalapril (−14.9 mL per minute) versus telmisartan (−17.9 mL per minute). Additionally, there were numerically more cases of congestive heart failure (9 versus 7) and non-fatal myocardial infarctions (9 versus 6) on telmisartan versus enalapril. Thus, despite greater blood pressure control, telmisartan does not produce better cardiovascular protection or renoprotection compared to enalapril. This is intriguing as perindopril, but not enalapril, has been shown to reduce cardiovascular events in patients with documented coronary heart disease.2,20
In regards to the ONTARGET trial, myocardial infarctions were numerically lower on ramipril (4.8%) versus telmisartan (5.2%) as were hospitalizations for heart failure (4.1% versus 4.6%, respectively).21 Thus, ONTARGET does not necessarily prove that telmisartan is equal to ramipril, especially when blood pressure was significantly lower on telmisartan. Additionally, ramipril significantly slowed the decline in estimated glomerular filtration rate versus telmisartan (P<0.0001), despite telmisartan leading to significantly greater reductions in ambulatory blood pressure.22 These results do not support a “comparable cardiovascular protection” with ARBs versus ACE-Is, especially when blood pressure control was not comparable. In ONTARGET, telmisartan was not compared against placebo, and a placebo-controlled trial is the gold-standard to test if a medication provides cardiovascular protection. These data are unfortunately lacking with telmisartan. Indeed, to our knowledge, telmisartan has no data versus placebo showing a significant reduction in all-cause mortality or myocardial infarctions. In fact, we are unaware of a single trial testing any ARB that has showed a significant reduction in all-cause mortality or myocardial infarctions versus placebo or active therapy. This is supported by several meta-analyses showing that ACE-inhibitors but not ARBs reduce all-cause mortality and myocardial infarctions.23–27
In a direct comparison trial in hypertensive patients, perindopril, but not telmisartan, significantly improved endothelial function (eg, decreased von Willebrand factor), provided anti-platelet effects (eg, decreased soluble P- selectin and soluble glycoprotein V), and produced profibrinolytic activity (eg, decrease in plasminogen activator inhibitor type 1 and tissue type plasminogen activator antigens).28 It was concluded that perindopril, but not telmisartan, provides vasculoprotective, anti-platelet and profibrinolytic effects. These pleiotropic effects may be important for perindopril’s ability to reduce cardiovascular morbidity and mortality. This is supported by another trial, where only perindopril, but not telmisartan, improved conduit artery endothelium-dependent vasodilation.29 Thus, head-to-head trials do not support equivalent cardiovascular effects with perindopril versus telmisartan.
In regards to “ARBs having fewer adverse effects and better patient compliance,”1 perindopril has demonstrated extremely low rates of cough in several large randomized trials.2,30 In Perindopril and Remodeling in Elderly with Acute Myocardial Infarction (PREAMI), Perindopril pROtection aGainst REcurrent Stroke Study, (PROGRESS), and EUROPA, perindopril was associated with a low rate of withdrawal due to cough (1.6%, 2.2%, and 2.7%, respective).2,30,31 In ONTARGET, cough was significantly increased with ramipril versus telmisartan (P<0.001). Importantly, other ACE-Is have shown a higher incidence of cough as compared to perindopril.32,33 In ONTARGET, telmisartan significantly increased hypotensive symptoms compared to ramipril (P<0.001). Both PROGRESS and EUROPA have shown excellent tolerability with perindopril, with low rates of withdrawals due to hypotension (2.1% and 1.0%, respectively).2,31 Additionally, perindopril has also shown less first-dose hypotension compared to other ACE-Is,34–36 suggesting that ARBs may not necessarily have fewer adverse events and better tolerability compared to ACE-Is, especially in regards to hypotension. Thus, the purported notion that telmisartan is better tolerated than ACE-Is, is not clear-cut, especially in regards to perindopril.
Regarding comparison trials for blood pressure lowering, in the only head-to-head randomized study comparing full-dose therapy of the two agents, perindopril (10 mg) as compared to telmisartan (80 mg) significantly reduced 24 hour systolic blood pressure (−22 versus −15 mmHg) and central aortic blood pressure (30% versus 14%).37 Central and ambulatory blood pressure levels are well recognized as better prognostic indicators compared to brachial blood pressure measurements.38,39 This may partly explain the disparate effects seen with perindopril and telmisartan on cardiovascular outcomes. These data are consistent with a meta-analysis showing that ARBs have a very shallow dose-response effect on ambulatory blood pressure.40
In summary, as compared to placebo, perindopril but not telmisartan has been shown to reduce major cardiovascular events. A broad amount of data support the blood-pressure independent benefits of ACE-Is, especially in regards to perindopril. Numerous meta-analyses now confirm that ACE-Is, but not ARBs, reduce the rate of all-cause mortality and myocardial infarctions. As compared to other ACE-Is, perindopril has been shown to have fewer adverse side effects, including lower rates of cough and first-dose hypotension. Due to perindopril’s long history of cardiovascular protection and enhanced tolerability, it should be a first-choice ACE-I. Moreover, ACE-Is, as compared to ARBs, should be considered first-line antihypertensives, with telmisartan being no exception.
Footnotes
Disclosure
Dr DiNicolantonio received honorarium from Servier for preparation of this manuscript. Dr O’Keefe declares no conflicts of interest. Servier provided Table 1.
References
- 1.Wang JG, Pimenta E, Chwallek F. Comparative review of the blood pressure-lowering and cardiovascular benefits of telmisartan and perindopril. Vasc Health Risk Manag. 2014;10:189–200. doi: 10.2147/VHRM.S59429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators 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. 2003;362(9386):782–788. doi: 10.1016/s0140-6736(03)14286-9. [DOI] [PubMed] [Google Scholar]
- 3.Ferrari R, Fox K. Insight into the mode of action of ACE inhibition in coronary artery disease: the ultimate ‘EUROPA’ story. Drugs. 2009;69(3):265–277. doi: 10.2165/00003495-200969030-00003. [DOI] [PubMed] [Google Scholar]
- 4.DiNicolantonio JJ, Lavie CJ, O’Keefe JH. Not All Angiotensin-Converting Enzyme Inhibitors Are Equal: Focus on Ramipril and Perindopril. Postgrad Med. 2013;125(4):154–168. doi: 10.3810/pgm.2013.07.2687. [DOI] [PubMed] [Google Scholar]
- 5.Aseeva OA. Coversyl: At the core of cardiovascular disease prevention and treatment. Medicographia. 2009;31(1):69–76. [Google Scholar]
- 6.Remme WJ, Deckers JW, Fox KM, Ferrari R, Bertrand M, Simoons ML, EUROPA Investigators Secondary prevention of coronary disease with ACE inhibition – does blood pressure reduction with perindopril explain the benefits in EUROPA? Cardiovasc Drugs Ther. 2009;23(2):161–170. doi: 10.1007/s10557-008-6143-6. [DOI] [PubMed] [Google Scholar]
- 7.Ceconi C, Fox KM, Remme WJ, et al. ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT. Cardiovasc Res. 2007;73(1):237–246. doi: 10.1016/j.cardiores.2006.10.021. [DOI] [PubMed] [Google Scholar]
- 8.Mancia G, Parati G, Bilo G, et al. Ambulatory blood pressure values in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) Hypertension. 2012;60(6):1400–1406. doi: 10.1161/HYPERTENSIONAHA.112.199562. [DOI] [PubMed] [Google Scholar]
- 9.Poulter NR, Wedel H, Dahlöf B, et al. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) Lancet. 2005;366(9489):907–913. doi: 10.1016/S0140-6736(05)67186-3. [DOI] [PubMed] [Google Scholar]
- 10.Williams B, Lacourcière Y, Schumacher H, Gosse P, Neutel JM. Antihypertensive efficacy of telmisartan vs ramipril over the 24-h dosing period, including the critical early morning hours: a pooled analysis of the PRISMA I and II randomized trials. J Hum Hypertens. 2009;23(9):610–619. doi: 10.1038/jhh.2009.4. [DOI] [PubMed] [Google Scholar]
- 11.Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. 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. 2000;342(3):145–153. doi: 10.1056/NEJM200001203420301. [DOI] [PubMed] [Google Scholar]
- 12.Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet. 1993;342(8875):821–828. [No authors listed] [PubMed] [Google Scholar]
- 13.Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators. Yusuf S, Teo K, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008;372(9644):1174–1183. doi: 10.1016/S0140-6736(08)61242-8. [DOI] [PubMed] [Google Scholar]
- 14.Yusuf S, Diener HC, Sacco RL, et al. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med. 2008;359(12):1225–1237. doi: 10.1056/NEJMoa0804593. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Wang W, Ma LY, Liu MB, et al. Effects of amlodipine plus telmisartan or amlodipine plus amiloride regimen on blood pressure control in hypertensive patients: preliminary report of Chinese Hypertension Intervention Efficacy (CHIEF) trial. ESH congress, oral presentation, Milan 2013. Cardiotimes; 2013. [Accessed July 31, 2014]. Available from: http://www.cardiotimes.com/?s=chief. [PubMed] [Google Scholar]
- 16.Tropeano AI, Boutouyrie P, Pannier B, et al. Brachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives. Hypertension. 2006;48(1):80–86. doi: 10.1161/01.HYP.0000224283.76347.8c. [DOI] [PubMed] [Google Scholar]
- 17.Blood Pressure Lowering Treatment Trialists’ Collaboration. Turnbull F, Neal B, Pfeffer M, et al. Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system. J Hypertens. 2007;25(5):951–958. doi: 10.1097/HJH.0b013e3280bad9b4. [DOI] [PubMed] [Google Scholar]
- 18.Turnbull F, Blood Pressure Lowering Treatment Trialists’ Collaboration Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362(9395):1527–1535. doi: 10.1016/s0140-6736(03)14739-3. [DOI] [PubMed] [Google Scholar]
- 19.Barnett AH, Bain SC, Bouter P, et al. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004;351(19):1952–1961. doi: 10.1056/NEJMoa042274. [DOI] [PubMed] [Google Scholar]
- 20.Nissen SE, Tuzcu EM, Libby P. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA. 2004;292(18):2217–2225. doi: 10.1001/jama.292.18.2217. [DOI] [PubMed] [Google Scholar]
- 21.ONTARGET Investigators. Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–1559. doi: 10.1056/NEJMoa0801317. [DOI] [PubMed] [Google Scholar]
- 22.Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372(9638):547–553. doi: 10.1016/S0140-6736(08)61236-2. [DOI] [PubMed] [Google Scholar]
- 23.Strauss MH, Hall AS. Angiotensin Receptor Blockers May Increase Risk of Myocardial Infarction Unraveling the ARB-MI Paradox. Circulation. 2006;114(8):838–854. doi: 10.1161/CIRCULATIONAHA.105.594986. [DOI] [PubMed] [Google Scholar]
- 24.van Vark LC, Bertrand M, Akkerhuis KM, et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J. 2012;33(16):2088–2097. doi: 10.1093/eurheartj/ehs075. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Cheng J, Zhang W, Zhang X, et al. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis. JAMA Intern Med. 2014;174(5):773–785. doi: 10.1001/jamainternmed.2014.348. [DOI] [PubMed] [Google Scholar]
- 26.Wu HY, Huang JW, Lin HJ, et al. Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis. BMJ. 2013;347:f6008. doi: 10.1136/bmj.f6008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Savarese G, Costanzo P, Cleland JG, et al. A meta-analysis reporting effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients without heart failure. J Am Coll Cardiol. 2013;61(2):131–142. doi: 10.1016/j.jacc.2012.10.011. [DOI] [PubMed] [Google Scholar]
- 28.Remková A, Kratochvíl’ová H, Durina J. Impact of the therapy by renin-angiotensin system targeting antihypertensive agents perindopril versus telmisartan on prothrombotic state in essential hypertension. J Hum Hypertens. 2008;22(5):338–345. doi: 10.1038/sj.jhh.1002328. [DOI] [PubMed] [Google Scholar]
- 29.Ghiadoni L, Magagna A, Versari D, et al. Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension. 2003;41(6):1281–1286. doi: 10.1161/01.HYP.0000070956.57418.22. [DOI] [PubMed] [Google Scholar]
- 30.Ferrari R, Perindopril and Remodeling in Elderly with Acute Myocardial Infarction Investigators Effects of angiotensin-converting enzyme inhibition with perindopril on left ventricular remodeling and clinical outcome: results of the randomized Perindopril and Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) Study. Arch Intern Med. 2006;166(6):659–666. doi: 10.1001/archinte.166.6.659. [DOI] [PubMed] [Google Scholar]
- 31.PROGRESS Collaborative Group Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033–1041. doi: 10.1016/S0140-6736(01)06178-5. [DOI] [PubMed] [Google Scholar]
- 32.Tumanan-Mendoza BA, Dans AL, Villacin LL, et al. Dechallenge and rechallenge method showed different incidences of cough among four ACE-Is. J Clinic Epidemiol. 2007;60(6):547–553. doi: 10.1016/j.jclinepi.2006.06.017. [DOI] [PubMed] [Google Scholar]
- 33.Yesil S, Yesil M, Bayata S, Postaci N. ACE inhibitors and cough. Angiology. 1994;45(9):805–808. doi: 10.1177/000331979404500908. [DOI] [PubMed] [Google Scholar]
- 34.Vítovec J, Spinar J. First-dose hypotension after angiotensin-converting enzyme (ACE) inhibitors in chronic heart failure: a comparison of enalapril and perindopril. Slovak Investigator Group. Eur J Heart Fail. 2000;2(3):299–304. doi: 10.1016/s1388-9842(00)00095-7. [DOI] [PubMed] [Google Scholar]
- 35.Reid JL, MacFadyen RJ, Squire IB, Lees KR. Blood pressure response to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure. Am J Cardiol. 1993;71(17):57E–60E. doi: 10.1016/0002-9149(93)90954-b. [DOI] [PubMed] [Google Scholar]
- 36.Lau CP, Tse HF, Ng W, et al. Comparison of perindopril versus captopril for treatment of acute myocardial infarction. Am J Cardiol. 2002;89(2):150–154. doi: 10.1016/s0002-9149(01)02191-9. [DOI] [PubMed] [Google Scholar]
- 37.Nedogoda SV, Ledyaeva AA, Chumachok EV, et al. Randomized trial of perindopril, enalapril, losartan and telmisartan in overweight or obese patients with hypertension. Clin Drug Investig. 2013;33(8):553–561. doi: 10.1007/s40261-013-0094-9. [DOI] [PubMed] [Google Scholar]
- 38.Roman MJ, Devereux RB, Kizer JR, et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study. Hypertension. 2007;50(1):197–203. doi: 10.1161/HYPERTENSIONAHA.107.089078. [DOI] [PubMed] [Google Scholar]
- 39.Verdecchia P. Prognostic value of ambulatory blood pressure: current evidence and clinical implications. Hypertension. 2000;35(3):844–851. doi: 10.1161/01.hyp.35.3.844. [DOI] [PubMed] [Google Scholar]
- 40.Makani H, Bangalore S, Supariwala A, Romero J, Argulian E, Messerli FH. Antihypertensive efficacy of angiotensin receptor blockers as monotherapy as evaluated by ambulatory blood pressure monitoring: a meta-analysis. Eur Heart J. 2014;35(26):1732–1742. doi: 10.1093/eurheartj/eht333. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Patel A, ADVANCE Collaborative Group. MacMahon S, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370(9590):829–840. doi: 10.1016/S0140-6736(07)61303-8. [DOI] [PubMed] [Google Scholar]