Evaluating the Impact of Mono- and Combination Antihypertensive Therapy with Dihydropyridine and Non-dihydropiridine Calcium Channel Blockers on the Parameters of Office Blood Pressure and Blood Pressure in Daily Monitoring in Patients with Mild to Modera

Yu.M. Sirenko, O.L. Rekovets, A.S. Dobrokhod


Introduction. The choice of treatment for arterial hypertension (AH) is based on the previous experience of using the drugs in a specific patient, profiles of cardiovascular risk, the presence of target organ damage, cardiovascular diseases, kidney diseases and diabetes mellitus. Typically, one patient has multiple risk factors, so the treatment of AH should be differentiated, often resorting to combination therapy. The advantage of combination therapy is that the simultaneous use of two different drugs is not only reduce the blood pressure (BP) more actively, but also provides the impact on different pathogenic mechanisms of hypertension. This enables to more effectively prevent target organ damage, as well as reduce side effects. Objective. This study was aimed to compare the effectiveness of lerkanidipin and diltiazem combination at different doses in patients with mild to moderate AH in terms of the effects on office BP and BP in daily monitoring.
Materials and methods. The study included 123 patients with mild to moderate AH: the average office systolic (SBP)/diastolic BP (DBP) — 149.12/91.92 ± 1.42/0.93 mmHg. Average age of patients was 51.83 ± 0.86 yearss. All patients were divided into the groups of therapy. The first group (n = 20) — patients received diltiazem at a dose of 240 mg per day in two divided doses. The second group (n = 20) — patients were administered lercanidipin 20 mg once daily. The third group (n = 22) — patients received non-fixed combination of 20 mg lercanidipin and 240 mg diltiazem a day. The fourth group (n = 20) — patients were administered non-fixed combination of 10 mg lercanidipin and 240 mg diltiazem a day. The fifth group (n = 21) — patients received non-fixed combination of 10 mg lercanidipin and 120 mg diltiazem per day. The sixth group (n = 20) — patients were administered non-fixed combination of 20 mg lercanidipin and 120 mg diltiazem a day. All patients at baseline in and end of treatment underwent the following studies: measurement of body weight and height, calculation of body mass index. We have carried out office SBP, DBP and heart rate measurement, ambulatory BP monitoring (ABPM), biochemical blood assay, which included determination of total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, atherogenic index. Duration of treatment was 1 month.
Results. After analyzing all the data, it was found that the indices of office SBP and DBP significantly decreased in patients with both mild and moderate hypertension in all groups almost equally. After 1 month of treatment: in the group of diltiazem 240 mg, office SBP/DBP was significantly decreased by 9.94/9.89 mmHg; in the group of 20 mg lercanidipine — by 12.35/8.18 mmHg; in the group of combination «ercanidipine 20 mg/diltiazem 240 mg» — by 12.75/8.19 mmHg; in the group of combination «lercanidipine 10 mg/diltiazem 240 mg» — by 11.60/8.33 mmHg; in the group of combination «lercanidipine 10 mg/diltiazem 120 mg» — by 11.68/9.84 mmHg; in the group of combination «lercanidipine 20 mg/diltiazem 120 mg» — by 13.88/9.76 mmHg. That is, all selected treatment regimens were equally effective in reducing office BP. According to the data of ABPM, combination therapy based on lercanidipine and diltiazem was as effective as the treatment on the basis of monotherapy with lercanidipine and diltiazem: in diltiazem 240 mg group, 24SBP/DBP decreased significantly by 11.92/7.22 mmHg, in a group of lercanidipine 20 mg — by 8.65/9.06 mmHg; in the group of combination «lercanidipine 20 mg/diltiazem 240 mg» — by 6.10/6.94 mmHg; in the group of combination «lercanidipine 10 mg/diltiazem 240 mg» — by 8.96/5.54 mm Hg; in the group of combination «lercanidipine 10 mg/diltiazem 120 mg» — by 7.21/5.47 mmHg; in the group of combination «lercanidipine 20 mg/diltiazem 120 mg» — by 6.81/7.89 mmHg. So, all selected treatment regimens were equally effective in reducing blood pressure daily. Achieving the target levels of office BP and BP at ABPM was the same in all treatment groups. In the group of diltiazem 240 mg both office BP and BP in ABPM was achieved in 72.23 % of patients. In lercanidipine group, both office BP and BP in ABPM was achieved in 76.47 % of patients. In the group of combination «lercanidipine 20 mg/diltiazem 240 mg», target office BP target was achieved in 56.25 % of patients, and target BP in ABPM — in 62.50 % of patients. In the group of combination «lercanidipine 10 mg/diltiazem 240 mg», target office BP was achieved in 66.67 % of patients, and target BP in ABPM — in 73.34 % of patients. In the group of combination «lercanidipine 10 mg/diltiazem 120 mg», target office BP was achieved in 52.63 % of patients, and target BP in ABPM — in 78.95 % of patients. In the group of combination «lercanidipine 20 mg/diltiazem 120 mg», target office BP was achieved in 82.35 % of patients, and target BP in ABMP — in 52.94 % of patients.
Conclusion. Treatment based on both monotherapy and combination of lercanidipin and diltiazem was effective in reducing both office BP and BP in daily monitoring. Due to better tolerability of lercanidipin 20 mg daily and low-dose combination of lercanidipin10 mg and diltiazem 120 mg, these strategies can be recommended for future treatment of patients with mild to moderate AH.


arterial hypertension; lercanidipin; diltiazem; office blood pressure


2007 European Society of Hypertension — European Society of Cardiology guidelines for management of arterial hypertension // J.Hypertension. — 2007. — Vol. 25. — P. 1105-1187.

Raicu M., Pojoga L., Simionescu N., Simionescu M. Diffe­rential effect of two calcium channel blockers nifedipine and diltiazem on atherogenesis in hypercholesterolemic hamster // J. Submicrosc. Cytol. Pathol. — 1996. — Vol. 28(2). — P. 265-275.

Richard S. Vascular effects of calcium channel antagonists: new evidence // Drugs. — 2005. — Vol. 65(2). — P. 1-10.

Scholze J.E. Differential therapy with calcium antagonists // Herz. — 2003. — Vol. 28(8). — P. 754-763.

Horwitz L.D., Weinberger H.D., Clegg L.Comparison of amlodi­pine and long-acting diltiazem in the treatment of mild or moderate hypertension // Am. J. Hypertens. — 1997. — Vol. 10(11). — P. 1263-1269.

Karaca I., Coşkun N., Yavuzkir M., Ilkay E., Dağli N., Işik A., Balin M., Akbulut M., Arslan N. Effect of diltiazem and metoprolol on left atrial appendix functions in patients with nonvalvular chronic atrial fibrillation // Anadolu Kardiyol. Derg. — 2007. — Vol. 7(1). — P. 37-41.

Kawano Y., Makino Y., Okuda N., Takishita S., Omae T. Effects of diltiazem retard on ambulatory blood pressure and heart rate variability in patients with essential hypertension // Blood Press. Monit. — 2000. — Vol. 5(3). — P. 181-185.

Luk J.H., Walsh B., Yasbin P. Safety and efficacy of prehospital diltiazem // West J. Emerg. Med. — 2013. — Vol. 14(3). — P. 296-300.

Bevan R.D.1, Bevan J.A., Frazee J.G. Diltiazem protects against functional changes in chronic cerebrovasospasm in monkeys // Stroke. — 1988. — Vol. 19(1). — P. 73-79.

Wright J.T. Jr., Sica D.A., Gana T.J., Bohannon K., Pascual L.G., Albert K.S. Antihypertensive efficacy of night-time graded-release diltiazem versus morning amlodipine in African Americans // Am. J. Hypertens. — 2004. — Vol. 17(9). — P. 734-742.

Watts R.W., Wing L.M. A placebo-controlled comparison of diltiazem and amlodipine monotherapy in essential hypertension using 24-hour ambulatory monitoring // Blood Press. — 1998. — Vol. 7(1). — P. 25-30.

Whelton A., Eff J., Magner D.J. Sustained antihypertensive activity of diltiazem SR: double-blind, placebo-controlled study with 24-hour ambulatory blood pressure monitoring // J. Clin. Pharmacol. — 1992. — Vol. 32(9). — P 808-815.

Pool P.E., Massie B.M., Venkataraman K., Hirsch A.T., Samant D.R., Seagren S.C., Gaw J., Salel A.F., Tubau J.F. Diltiazem as monotherapy for systemic hypertension: a multicenter, randomized, placebo-controlled trial // Am. J. Cardiol. — 1986. — Vol. 57(4). — P. 212-217.

Chrysant S.G., Miller E. Effects of atenolol and diltiazem-SR on exercise and pressure load in hypertensive patients // Clin. Cardiol. — 1994. — Vol. 17(12). — P. 670-674.

Betocchi S., Piscione F., Losi M.A., Pace L., Boccalatte M., Perrone-Filardi P., Cappelli-Bigazzi, Briguori C., Manganelli F., Ciampi Q., Salvatore M., Chiariello M. Effects of diltiazem on left ventricular systolic and diastolic function in hypertrophic cardiomyopathy // Am. J. Cardiol. — 1996. — Vol. 78(4) — P. 451-457.

Chern M.S., Lin F.C., Wu D. Comparison of clinical efficacy and adverse effects between extended-release felodipine and slow-release diltiazem in patients with isolated systolic hypertension // Changgeng Yi Xue Za Zhi. — 1999. — Vol. 22(1). — P. 44-51.

Coca A., Sobrino J., Soler J., Módol J., Palos M.A., Mínguez A., Esqúe J., Plana J., Cases M., Closas J., de la Sierra A. Trough-to-peak ratio and circadian blood pressure profile after treatment with once-daily extended-release diltiazem, 240 mg, in patients with mild-to-moderate essential hypertension // J. Cardiovasc. Pharmacol. — 1997. — Vol. 29(3). — P. 316-322.

Barrios V., Navarro A., Esteras A., Luque M., Romero J., Tamargo J., Prieto L., Carrasco J.L., Herranz I., Navarro-Cid J., Ruilope L.M. Investigators of ELYPSE Study (Eficaciade Lercanidipino Perfilde Seguridad). Antihypertensive efficacy and tolerability of lercanidipine in daily clinical practice. The ELYPSE Study. Eficacia de Lercanidipino y suPerfil de Seguridad // Blood Press. — 2002. — Vol. 11(2). — P. 95-100.

Borghi C. Lercanidipine in hypertension // Vasc. Health. Risk. Manag. — 2005. — Vol. 1(3). — P. 173-182.

Burnier M., Pruijm M., Wuerzner G. Treatment of essential hypertension with calcium channel blockers: what is the place of lercanidipine? // Expert. Opin. Drug. Metab. Toxicol. — 2009. — Vol. 5(8). — P. 981-987.

Burnier M. Renal protection with calcium antagonists: the role of lercanidipine // Curr. Med. Res. Opin. — 2013. — Vol. 29(12). — P. 1727-1735.

Corsini A., Bonfatti M., Quarato P., Accomazzo M.R., Raite­ri M., Sartani A., Testa R., Nicosia S., Paoletti R., Fumagalli R. ­Effect of the new calcium antagonist lercanidipine and its enantiomers on the migration and proliferation of arterial myocytes // J. Cardiovasc. Pharmacol. — 1996. — Vol. 28(5). — P. 687-694.

Burnier M. Renal protection with calcium antagonists: the role of lercanidipine // Curr. Med. Res. Opin. — 2013. — Vol. 29(12). — P. 1727-1735.

Cesarone M.R., Incandela L., Ledda A., De Sanctis M.T., Steigerwalt R., Pellegrini L., Bucci M., Belcaro G., Ciccarelli R. Pressure and microcirculatory effects of treatment with lercanidipine in hypertensive patients and in vascular patients with hypertension // Angiology. — 2000. — Vol. 51(8 Pt 2). — P. 53-63.

Corsini A., Accomazzo M.R., Canavesi M., Sartani A., Testa R., Catapano A.L., Fumagalli R., Paoletti R., Bernini F. The new calcium antagonist lercanidipine and its enantiomers affect major processes of atherogenesis in vitro: is calcium entry involved? // Blood Press Suppl. — 1998. — Vol. 2. — P. 18-22.

Farah R., Shurtz-Swirski R., Khamisy-Farah R. Lercanidipine effect on polymorphonuclear leukocyte-related inflammation and insulin resistance in essential hypertension patients // Cardiol. Ther. — 2012. — Vol. 1(1). — P. 4.

Cicero A.F., Gerocarni B., Rosticci M., Borghi C. Blood pressure and metabolic effect of a combination of lercanidipine with different antihypertensive drugs in clinical practice // Clin. Exp. Hypertens. — 2012. — Vol. 34(2) — P. 113-117.

Haller H., Cosentino F., Lüscher T.F. Endothelial dysfunction, hypertension and atherosclerosis. A review of the effects of lacidipine // Drugs R. D. — 2002. — Vol. 3(5) — P. 311-323.

Herbette L.G., Vecchiarelli M., Sartani A., Leonardi A. Lercanidipine: short plasma half-life, long duration of action and high cholesterol tolerance. Updated molecular model to rationalize its pharmacokinetic properties // Blood Press Suppl. — 1998. — Vol. 2. — P. 10-17.

McClellan K.J., Jarvis B. Lercanidipine: a review of its use in hypertension // Drugs. — 2000. — Vol. 60(5). — P. 1123-1140.

Meier P., Burnier M. Lercanidipine, a third generation calcium antagonist. Which advantages? // Rev. Med. Suisse. — 2006. — Vol. 2(78). — P. 2047-2050, 2052-2053.

Omboni S., Zanchetti A. Antihypertensive efficacy of lercanidipine at 2.5, 5 and 10 mg in mild to moderate essential hypertensives assessed by clinic and ambulatory blood pressure measurements. Multicenter Study Investigators // J. Hypertens. — 1998. — Vol. 16(12 Pt 1). — P. 1831-1838.

Sakurai-Yamashita Y., Harada N., Niwa M. Lercanidipine rescues hippocampus pyramidal neurons from mild ischemia-induced delayed neuronal death in SHRSP // Cell. Mol. Neurobiol. — 2011. — Vol. 31(4). — P. 561-567.

Yeh J.L., Hsu J.H., Liang J.C., Chen I.J., Liou S.F. Lercanidipine and labedipinedilol-A attenuate lipopolysaccharide/interferon-γ-induced inflammation in rat vascular smooth muscle cells through inhibition of HMGB1 release and MMP-2, 9 activities // Atherosclerosis. — 2013. — Vol. 226(2). — P. 364-372.

Zanchetti A., Bond M.G., Hennig M., Neiss A., Mancia G., Dal Palù C., Hansson L., Magnani B., Rahn K.H., Reid J.L., Rodicio J., Safar M., Eckes L., Rizzini P. European Lacidipine Study on Atherosclerosis investigators. Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis: principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, long-term trial // Circulation. — 2002. — Vol. 106(19). — P. 2422-2427.

Fumiharu Togo and Masaya Takahashi. Heart Rate Variability in Occupational Health — A Systematic Review // Industrial. Health. — 2009. — Vol. 47. — P. 589-602.

Piccirillo G., Fimognari F.L., Munizzi M.R., Bucca C., Cacciafesta M., Marigliano V. Age-depended influence on heart rate varia­bility in salt-sensitive hypertensive subjects // J. Am. Geriatr. Soc. — 1996. — Vol. 44(5). — P. 530-538.

Salo T.M., Viikari J.S., Antila K.J., Voipio-Pulkki L.M., Jalonen J.O., Valimaki I.A. Antihypertensive treatment and hert rate variability in diabetic patients: role of cardiac autonomic neuropathy // J. Auton. Nerv. Syst. — 1996. — Vol. 60(1–2). — P. 61-70.

Wang H.B., Shi Q., Zhang C. Effects of heart rate variability and smoothness index on reversal of hypertensive left ventricular hypertrophy // Zhonghua Yi Xue Za Zhi. — 2011. — Vol. 91(12). — P. 832-835.

Lotufo P.A., Valiengo L., Bensenor I.M., Brunoni A.R. A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs // Epilepsia. — 2012. — Vol. 53(2). — P. 272-282.

Li L.X., Tang W., Chen B.J., Wang T. Cross-sectional study of relation between blood pressure and heart rate variability in patients with peritoneal dialysis // Beijing Da Xue Xue Bao. — 2011. — Vol. 43(6). — P. 849-854.

Weston K.S., Sacre J.W., Jellis C.L., Coombes JS. Contribution of autonomic dysfunction to abnormal exercise blood pressure in type 2 diabetes mellitus // J. Sci Med. Sport. — 2013 — Vol. 16(1). — P. 8-12.

Zhou Y., Xie G., Wang J., Yang S. Cardiovascular Risc Factors Significantly Correlate With Automatic Nervous System Activity in Children // Can. J. Cardiol. — 2012. — Vol. 28(4). — P. 477-482.

Evrengul H., Tanriverdi H., Kose S., Amasyali B., Kilic A., Celik T., Turhan H. The relationship between heart rate recovery and heart rate variability in coronary artery disease // Ann. Noninvasive Electrocardiol. — 2006. — Vol. 11(2). — P. 154-162.

Eryonucu B., Bilge M., Guler N., Uygan I. The effect of autonomic nervous system activity on exaggerated blood pressure response to exercise: evaluation by heart rate variability // Acta Cardiol. — 2000. — Vol. 55(3). — P. 181-185.

Piccrillo G., Elvira S., Viola E., Bucca C., Durante M., Raganto P., Marigliano V. Automatic modulation of heart rate and blood pressure in hypertensive subjects with symptoms of anxiety // Clin. Sci (Lond). — 1998. — Vol. 95(1). — P. 43-52.

Piccrillo G., Vetta F., Viola E., Santagada E., Ronzoni S., Cacciafesta M., Marigliano V. Heart rate and blood pressure varia­bility in obese normotensive subjects // Int. J. Obes. Relat. Metab. Disord. — 1998. — Vol. 22(8). — P. 741-750.

Piccrillo G., Munizzi M.R., Fimognari F.L., Marigliano V. Heart rate variability in hypertensive subjects // Int. J. Cardiol. — 1996. — Vol. 53(3). — P. 291-298.

Valera B., Dewailly E., Poirier P.P., Counil E., Suhas E. Influence of mercury exposure on blood pressure, resting heart rate and heart rate variability in French Polynesians: a cross-sectional study // Envaironmental Health. — 2011. — Vol. 10. — P. 99.

Tsuji H., Venditti Jr., Manders E.S., Evans J.C., Larson M.J., Feldman C.L., Levy D. Reduced heart rate variability and mortality risk in elderly cohort. The Framingham // Circulation. — 1994. — Vol. 90. — P. 878-883.

Singh J.P., Larson M.G., Tsuji H., Evans J.C., O’Donnell C.J., Levy D. Reduced Heart Rate Variability and New-Onset Hypertension // Hypertension. — 1998. — Vol. 32. — P. 293-297.

Gyung-Mee Kim, Jong-Min Woo. Determination for Heart Rate Variability in a Normal Korean Population // Jn. Korean Med. Sci. — 2011. — Vol. 26(10). — P. 1293-1298.

Kinoshita H., Kuwahara K., Takano M., Arai Y., Kuwabara Y., Yasuno S. et al. T-Type Ca2+ Channel Blockade Prevents Sudden Death in Mice With Heart Failure // Circulation. — 2009. — Vol. 120. — P. 743-752.

Rachmani R., Levi Z., Zadok B.S., Ravid M. Losartan and lercanidipine attenuate low-density lipoprotein oxidation in patients with hypertension and type 2 diabetes mellitus: a randomized, prospective crossover study // Clin. Pharmacol. Ther. — 2002. — Vol. 72(3). — P. 302-307.

Huang Q., Li Y., Sheng C at all. 7B.09: Blood pressure lowering efficacy of amlodipine and nifedipine-gits in ambulatory hypertension // J. Hypertension. — 2015. — Vol. 33, Suppl. 1. — e94.

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