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Telmisartan Versus Angiotension-Converting Journal of Human Hypertension (2009) 23, 339–349 & 2009 Macmillan Publishers Limited All rights reserved 0950-9240/09 $32.00 www.nature.com/jhh ORIGINAL ARTICLE Telmisartan versus angiotension- converting enzyme inhibitors in the treatment of hypertension: a meta-analysis of randomized controlled trials Z Zou1,3, G-L Xi2,3, H-B Yuan1, Q-F Zhu1 and X-Y Shi1 1Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China and 2Center for New Drug Evaluation, Institute of Basic Medical Science, Second Military Medical University, Shanghai, People’s Republic of China Telmisartan and angiotensin-converting enzyme inhibi- 0.33–2.62). Telmisartan also showed a greater DBP tors (ACEIs) are both effective and widely used response rate than enalapril (relative risk (RR) 1.15, antihypertensive drugs targeting renin–angiotensin– 95% CI 1.05–1.26), ramipril (RR 1.34, 95% CI 1.11–1.61) aldosterone system. The study aimed to estimate the and perindopril (RR 1.22, 95% CI 1.05–1.41). There was efficacy and tolerability of telmisartan in comparison no statistical difference in DBP reduction or therapeutic with different ACEIs as monotherapy in the treatment of response rate between telmisartan and lisinopril (WMD hypertension. Cochrane Central Register of Controlled À0.30, 95% CI À0.65 to 0.05; RR 0.99, 95% CI 0.80–1.23, Trials, PubMed and Embase were searched for relevant respectively). Telmisartan had fewer drug-related studies. A meta-analysis of all randomized controlled adverse events than enalapril (RR 0.57, 95% CI 0.44–0.74), trials fulfilling the predefined criteria was performed. A ramipril (RR 0.44, 95% CI 0.26–0.75), lisinopril (RR 0.70, random-effect model was used to account for hetero- 95% CI 0.56–0.89) and perindopril (RR 0.52, 95% CI geneity among trials. Twenty-eight randomized con- 0.28–0.98). The meta-analysis indicates that telmisartan trolled trials involving 5157 patients were ultimately provides a superior BP control to ACEIs (enalapril, identified out of 721 studies. Telmisartan had a greater ramipril and perindopril) and has fewer drug-related diastolic blood pressure (DBP) reduction than enalapril adverse events and better tolerability in hypertensive (weighted mean difference (WMD) 1.82, 95% confidence patients. interval (CI) 0.66–2.99), ramipril (WMD 3.09, 95% CI Journal of Human Hypertension (2009) 23, 339–349; 1.94–4.25) and perindopril (WMD 1.48, 95% CI doi:10.1038/jhh.2008.132; published online 6 November 2008 Keywords: telmisartan; angiotensin II type 1 receptor blockers; angiotensin-converting enzyme inhibitors; antihyper- tensive agents Introduction Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers Hypertension is a major risk factor for myocardial (ARBs) are two kinds of effective and widely used infarction, congestive heart failure, stroke, end-stage 1 antihypentisive drugs targeting renin–angiotensin– renal disease and even sudden death. Benefits of aldosterone system. ACEIs prevent the generation of consistent reduction of blood pressure (BP) to 2 angiotensin II from angiotensin I, while ARBs exert prevent end-organ damages are well established. their vasodilatation effect at the receptor level by However, only 34% patients with hypertension are inhibiting the binding of angiotensin II to the type 1 adequately controlled to a BP of p140/90 mm Hg, receptors, irrespective of whether angiotensin II is despite the fact that the importance of BP control 3 generated by renin–angiotensin cascade or in local has been recognized. tissues by other pathways. The direct blockade of angiotensin II to the type 1 receptors might be more Correspondence: Professor X-Y Shi, Department of Anesthesio- effective than the indirect blockade of ACEIs. Unlike lgoy, Changzheng Hospital, Second Military Medical University, ACEIs, ARBs do not disrupt the degeneration of 415 Fengyang Road, Shanghai 200003, People’s Republic of other peptides such as bradykinin, which may cause China. persistent dry cough and angioedema. The ARB E-mail: [email protected] 3These authors contributed equally to this study. telmisartan is an orally active and potent nonpep- Received 1 August 2008; revised 5 October 2008; accepted 5 tide selective AT1 antagonist with a long terminal October 2008; published online 6 November 2008 elimination half-life of about 24 h in the patients Meta-analysis comparing telmisartan with ACEIs Z Zou et al 340 with hypertension.4 Telmisartan is an effective 2008). The search combined the terms related to antihypertensive agent that provides smooth control ‘telmisartan’ (‘Micardis’, ‘Pritor’) with the terms of BP, with a low rate of adverse events profile related to ACEIs (‘alacepril’, ‘benazepril’, ‘benaze- compared with placebo,4–6 and without cough that is prilat’, ‘captopril’, ‘ceranapril’, ‘cilazapril’, ‘cilaza- frequently associated with ACEIs.6 In addition, the prilat’, ‘delapril’, ‘enalapril’, ‘enalaprilat’, lipophilic nature of its molecule should enhance its ‘fosinopril’, ‘fosinoprilic acid’, ‘imidapril’, ‘libenza- tissue penetration compared with other ARBs.7 pril’, ‘lisinopril’, ‘moexipril’, ‘moveltipril’, ‘altio- Telmisartan 80 mg given once daily provides a better pril’, ‘omapatrilat’, ‘perindopril’, ‘perindoprilat’, BP control than losartan 50 mg or valsartan 80 mg.8,9 ‘quinapril’, ‘quinaprilat’, ‘ramipril’, ‘ramiprilat’, Telmisartan provides numerically greater weighted ‘rentiapril’, ‘saralasin’, ‘spirapril’, ‘temocapril average reductions of diastolic BP (DBP) and hydrochloride’, ‘teprotide’, ‘trandolapril’, ‘zofenopril’), systolic BP (SBP) than irbesartan and candesartan using Boolean operators and database-specific cilexetil.10 syntax. We also searched the reference lists of the The findings of the Ongoing Telmisartan Alone original reports and meta-analyses of studies invol- and in Combination with Ramipril Global Endpoint ving ARBs (retrieved through the electronic Trial (ONTARGET) show that the combination of searches) to identify studies, which had not yet telmisartan with ramipril is associated with more been included in the computerized databases. adverse events without an increase in benefits in patients with vascular disease or high-risk dia- betes.11 Aiming to evaluate which drug was more eligible for patients with hypertension, we under- Trials selection took a systematic review and meta-analysis to Studies meeting the following selection criteria determine the clinical efficacy and tolerability were included in this meta-analysis: (1) study of telmisartan in comparison with ACEIs as mono- design: prospective randomized controlled clinical therapy in the treatment of hypertension. trials; (2) population: patients with hypertension, with or without other diseases such as metabolic syndrome and chronic kidney diseases; (3) inter- Methods ventions: telmisartan versus ACEIs, used as mono- therapy and (4) outcome variables: at least one of BP, We tried to identify and include all randomized therapeutic BP response rates, mortality, cerebro- controlled trials carried out to assess the efficacy cardiovascular event rates, adverse events, with- and tolerability associated with the use of telmisar- drawal and cough was reported. Two reviewers (ZZ, tan compared with ACEIs in patients with hyper- GLX) independently assessed the eligibility of a trial tension. to be included in our meta-analysis, and this was checked by another author (XYS). To avoid duplica- Outcome measures tion, only the data from the latest series were The primary efficacy variable was the reduction included if the same group of patients were involved from the baseline to the end of treatment in clinical in different reports. DBP and SBP. Second efficacy variables included the following: therapeutic response rates of DBP and SBP (DBP o90 mm Hg and/or a reduction of X10 mm Hg, 24-h mean ambulatory DBP Data extraction o85 mm Hg and/or a reduction from baseline of Data were independently abstracted for each identi- X10 mm Hg; SBP o140 mm Hg and/or a reduction fied trials by two researchers (ZZ, GLX), and any of X10 mm Hg, 24-h mean ambulatory SBP disagreement was resolved by discussion. Data o130 mm Hg and/or a reduction from baseline of were extracted from each study with a predesigned X10 mm Hg); reductions from baseline in ambula- review form. The following data were included: the tory DBP and SBP in 24-h, the last 6-h, daytime and authors of each study, the year of publication, the night time periods; and rate of cerebro-cardiovascu- design of the trial, the duration of the study, the lar events. We also assessed the tolerability of the number of the patients, the age of the patients, sex, drugs by considering overall rates of withdrawal, baseline SBP/DBP values, end point SBP/DBP withdrawal for adverse events, the number of values, changes from baseline in SBP and DBP, the patients experiencing adverse events, and the ambulatory SBP and DBP values and therapeutic relationship between such events and the drugs response rates of SBP and DBP. In addition, we administered to patients. retrieved the number or proportion of adverse events, withdrawals, mortality and cerebro-cardio- vascular events. Only the data associated with Search strategy monotherapy were retrieved if the patients received We searched the Cochrane Central Register of monotherapy as well as a combination of other Controlled Trials (Cochrane Library Issue 2, 2008), antihypertensive drugs once they were reported PubMed (up to 7 June 2008), Embase (1980 to June separately.
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