Download PDF
Arzneimittelforschung 2008; 58(9): 435-440
DOI: 10.1055/s-0031-1296535
Cardiac Drugs · Cardiac Stimulants · Coronary Drugs
Editio Cantor Verlag Aulendorf (Germany)

Effects of Calcium Channel Blockers on Cardiac Events, Stroke and End-stage Renal Disease in Patients with Angina pectoris

Retrospective comparative study of benidipine, diltiazem and nifedipine
Ichiro Arioka
1   Division of Cardiovascular Surgery, Dohi Hospital, Hiroshima, Japan
,
Shunichiro Dohi
1   Division of Cardiovascular Surgery, Dohi Hospital, Hiroshima, Japan
,
Shizuyuki Dohi
1   Division of Cardiovascular Surgery, Dohi Hospital, Hiroshima, Japan
,
Kenya Sakai
2   Division of Cardiology, Dohi Hospital, Hiroshima, Japan
› Author Affiliations
Further Information

Publication History

Publication Date:
19 December 2011 (online)

    Permissions and Reprints

Abstract

Background and aim:

Calcium channel blockers (CCBs) have been reported to reduce the incidence of stroke in hypertensive patients. CCBs are also commonly used to treat patients with angina pectoris (AP). However, there are very few reports on their effects on cardiovascular events, including stroke and end-stage renal disease (ESRD), in patients with AP. This study was designed to assess the differences among CCBs regarding the occurrence of cardiovascular events in patients with AP.

Methods:

Clinical records of 226 patients with AP who had received treatment with CCBs in hospital from January 1, 1993 to December 31, 2006 were reviwed. The influence of patient characteristics and medication on the occurrence of cardiovascular events was evaluated (median follow-up period: 4.4 years). Of these 226 patients, 155 were treated with benidipine (CAS 91599-74-5), 36 with diltiazem (CAS 33286-22-5), and 35 were treated with nifedipine (CAS 21829-25-4).

Results:

Cox proportional hazard regression analysis showed that benidipine was the only CCB that significantly reduced the occurrence of cardiovascular events (HR=0.39, p<0.05). Benidipine treatment was associated with higher cardiovascular- and cardiac event-free rates than diltiazem treatment, and higher stroke- and ESRD-free rates than nifedipine.

Conclusion:

This study demonstrated that benidipine prevents the occurrence of cardiovascular events in patients with AP, suggesting that benidipine contributes to a favorable long-term prognosis of such patients.

Key words

Angina pectoris - Benidipine - Calcium channel blockers, cardiovascular events, prognostic effect - CAS 21829-25-4 - CAS 33286-22-5 - CAS 91599-74-5 - Coniel® - Diltiazem - Nifedipine
 

  • References

  • 1 Yui Y, Sumiyoshi T, Kodama K, Hirayama A, Nonogi H, Kan-matsuse K et al. Japan Multicenter Investigation for Cardiovascular Diseases-B Study Group. Comparison of nifedipine retard with angiotensin converting enzyme inhibitors in Japanese hypertensive patients with coronary artery disease: the Japan Multicenter Investigation for Cardiovascular Diseases-B (JMIC-B) randomized trial. Hypertens Res. 2004; 27: 181-191
    CrossrefPubMedGoogle Scholar
  • 2 Pristipino C, Beltrame JF, Finocchiaro ML, Hattori R, Fujita M, Mongiardo R et al. Major racial differences in coronary constrictor response between Japanese and Caucasians with recent myocardial infarction. Circulation. 2000; 101: 1102-1108
    CrossrefPubMedGoogle Scholar
  • 3 Shimokawa H, Nagasawa K, Irie T, Egashira S, Egashira K, Sagara T et al. Clinical characteristics and long-term prognosis of patients with variant angina. A comparative study between western and Japanese populations. Int J Cardiol. 1988; 18: 331-349
    CrossrefPubMedGoogle Scholar
  • 4 β-Blocker Heart Attack Trial Research Group. A randomized trial of propranolol in patients with acute myocardial infarction. II. Morbidity results. JAMA. 1983; 250: 2814-2819
    CrossrefPubMedGoogle Scholar
  • 5 Japanese beta-Blockers and Calcium Antagonists Myocardial Infarction (JBCMI) Comparison of the effects of beta blockers and calcium antagonists on cardiovascular events after acute myocardial infarction in Japanese subjects. Am J Cardiol. 2004; 93: 969-973
    CrossrefPubMedGoogle Scholar
  • 6 The Israeli Sprint Study Group Secondary prevention reinfarction Israeli nifedipine trial (SPRINT): A randomized intervention trial of nifedipine in patients with acute myocardial infarction. Eur Heart J. 1988; 9: 354-364
    PubMedGoogle Scholar
  • 7 Psaty BM, Heckbert SR, Koepsell TD, Siscovick DS, Raghunathan TE, Weiss NS et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA. 1995; 274: 620-625
    CrossrefPubMedGoogle Scholar
  • 8 Furberg CD, Psaty BM, Meyer JV. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. Circulation. 1995; 92: 1326-1331
    CrossrefPubMedGoogle Scholar
  • 9 Poole-Wilson PA, Lubsen J, Kirwan BA, van Dalen FJ, Wagener G, Danchin N et al. A Coronary disease Trial Investigating Outcome with Nifedipine gastrointestinal therapeutic system investigators. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial. Lancet. 2004; 364: 849-857
    CrossrefPubMedGoogle Scholar
  • 10 Pitt B, Byington RP, Furberg CD, Hunninghake DB, Mancini GB, Miller ME et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation. 2000; 102: 1503-1510
    CrossrefPubMedGoogle Scholar
  • 11 Japanese Society of Hypertension. Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2004). Hypertens Res. 2006; 29: S1-S105
    PubMedGoogle Scholar
  • 12 The Japanese Circulation Society, The Japanese College of Cardiology, The Japanese Association for Thoracic Surgery, The Japanese Society for Cardiovascular Surgery. Guideline for Surgical and Interventional Treatment of Valvular Heart Disease. Circ J. 2002; 66 (S4) 1325-1350
    PubMedGoogle Scholar
  • 13 Zhang X, Hintze TH. Amlodipine releases nitric oxide from canine coronary microvessels: an unexpected mechanism of action of a calcium channel-blocking agent. Circulation. 1998; 97: 576-580
    CrossrefPubMedGoogle Scholar
  • 14 Matsubara M, Yao K, Hasegawa K. Benidipine, a dihydropyridine-calcium channel blocker, inhibits lysophosphati-dylcholine-induced endothelial injury via stimulation of nitric oxide release. Pharmacol Res. 2006; 53: 35-43
    CrossrefPubMedGoogle Scholar
  • 15 Kitakaze M, Node K, Minamino T, Asanuma H, Kuzuya T, Hori M. A Ca channel blocker, benidipine, increases coronary blood flow and attenuates the severity of myocardial ischemia via NO-dependent mechanisms in dogs. J Am Coll Cardiol. 1999; 33: 242-249
    CrossrefPubMedGoogle Scholar
  • 16 Wang N, Minatoguchi S, Chen XH, Arai M, Uno Y, Lu C et al. Benidipine reduces myocardial infarct size involving reduction of hydroxyl radicals and production of protein kinase C-dependent nitric oxide in rabbits. J Cardiovasc Pharmacol. 2004; 43: 747-757
    CrossrefPubMedGoogle Scholar
  • 17 Karasawa A, Ikeda J, Yamada K, Kubo K, Oka T, Nakamizo N. Antihypertensive effects of the new calcium antagonist benidipine hydrochloride in conscious, renal-hypertensive dogs. Arzneimittel-Forschung (Drug Research). 1988; 38: 1695-1697
    PubMedGoogle Scholar
  • 18 Nomura M, Nakaya Y, Uemura E, Sawa Y, Iga A, Kageyama N et al. Effects of benidipine hydrochloride on autonomic nervous activity in hypertensive patients with high- and low-salt diets. Arzneimittel-Forschung (Drug Research). 2003; 53: 314-320
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Shimamoto H, Shimamoto Y. Benidipine counteracts sodium-induced alterations in systemic and regional hemodynamics. Blood Press. 1997; 6: 18-23
    CrossrefPubMedGoogle Scholar
  • 20 Yao K, Ina Y, Sonoda R, Nagashima K, Ohmori K, Ohno T. Protective effects of benidipine on hydrogen peroxide-induced injury in rat isolated hearts. J Pharm Pharmacol. 2003; 55: 109-114
    PubMedGoogle Scholar
  • 21 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: 1527-1535
    CrossrefPubMedGoogle Scholar
  • 22 Ikeda J, Yao K, Matsubara M. Effects of benidipine, a long-lasting dihydropyridine-Ca2+ channel blocker, on cerebral blood flow autoregulation in spontaneously hypertensive rats. Biol Pharm Bull. 2006; 29: 2222-2225
    CrossrefPubMedGoogle Scholar
  • 23 Kitayama J, Kitazono T, Ooboshi H, Takada J, Fujishima M, Ibayashi S. Long-term effects of benidipine on cerebral va-soreactivity in hypertensive rats. Eur J Pharmacol. 2002; 438: 153-158
    CrossrefPubMedGoogle Scholar
  • 24 Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004; 351: 1296-1305
    CrossrefPubMedGoogle Scholar
  • 25 Inoue S, Tomino Y. Effects of calcium antagonists in hypertensive patients with renal dysfunction: a prospective, randomized, parallel trial comparing benidipine and nifedipine. Nephrology (Carlton). 2004; 9: 265-271
    CrossrefPubMedGoogle Scholar
  • 26 Akizuki O, Inayoshi A, Kitayama T, Yao K, Shirakura S, Sasaki K et al. Blockade of T-type voltage-dependent Ca(2+) channels by benidipine, a dihydropyridine calcium channel blocker, inhibits aldosterone production in human adrenocortical cell line NCI-H295R. Eur J Pharmacol. 2008; 584: 424-434
    CrossrefPubMedGoogle Scholar
  • 27 Morikawa T, Okumura M, Konishi Y, Okada N, Imanishi M. Effects of benidipine on glomerular hemodynamics and proteinuria in patients with nondiabetic nephropathy. Hy-pertens Res. 2002; 25: 571-576
    CrossrefPubMedGoogle Scholar