The calcium-channel blockers are useful in treating a variety of cardiovascular disorders. Due to their antiischemic and spasmolytic properties, these agents have been studied in the prophylaxis and treatment of acute myocardial infarction. This article reviews this application with respect to reduction of mortality, infarct size, and reinfarction rate. Of the agents currently available for clinical use, nifedipine has been studied most extensively. This agent shows no beneficial effects in this setting and its use may in fact be harmful. Of the few trials that have been conducted with verapamil, none have shown decreased mortality. Verapamil may reduce infarct size although further confirmation is required. Diltiazem is the only agent that has been shown to have short- and long-term benefits in the patient with acute myocardial infarction. Proper patient selection is of utmost importance in ensuring successful therapy. In particular, those patients with non-Q-wave infarctions and/or normal left ventricular function can be expected to derive the most benefit in terms of reducing mortality and reinfarction rate associated with the acute event.
Get full access to this article
View all access options for this article.
References
1.
SowardAL, VanhaleweykGLJ, SerruysPW. The haemodynamic effects of nifedipine, verapamil and diltiazem in patients with coronary artery disease. A review.Drugs1986; 32: 66–101.
2.
WeinerDA. Calcium channel blockers.Med Clin North Am1988; 72: 83–115.
3.
TonkonM. Hemodynamic profiles of antianginal agents.Pharmacotherapy1987; 7: 72S–5S.
4.
ScriabineA. Current and potential indications for Ca2+ antagonists.Ration Drug Ther1987; 21: 1–7.
O'ROURKERA, WalshRA. Experience with calcium antagonist drugs in congestive heart failure.Am J Cardiol1987; 59: 64B–9B.
7.
ShubC, VlietstraRE, McgoonMD. Selection of optimal drug therapy for the patient with angina pectoris.Mayo Clin Proc1985; 60: 539–48.
8.
KhurmiNS, RafteryEB. A comparison of nine calcium antagonists and propranolol: exercise tolerance, heart rate and ST-segment changes in patients with chronic stable angina pectoris.Eur J Clin Pharmacol1987; 32: 539–48.
9.
FeldmanRL, PepineCJ, WhittleJ, ContiCR. Short- and long-term responses to diltiazem in patients with variant angina.Am J Cardiol1982; 49: 554–9.
ZemaMJ, PerlmutterS, MankesS, NikitopoulosC. Diltiazem treatment for the management of ischaemia in patients with poor left ventricular function: safety of long term administration.Br Heart J1987; 58: 512–7.
15.
PackerM, KesslerPD, LeeWH. Calcium-channel blockade in the management of severe chronic congestive heart failure: a bridge too far.Circulation1987; 75(suppl V): V56–64.
16.
LorellBH. Use of calcium channel blockers in hypertrophic cardiomyopathy.Am J Med1975; 78(suppl 2B): 43–54.
17.
MaronBJ, BonowRO, CannonRO, LeonMB, EpsteinSE. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (second of two parts).N Engl J Med1987; 316: 844–52.
DewoodMA, SporesJ, NotskeR. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction.N Engl J Med1980; 303: 897–902.
20.
MaseriA, L'ABBATEA, BaroldiG. Coronary vasospasm as a possible cause of myocardial infarction. A conclusion derived from the study of “preinfarction” angina.N Engl J Med1978; 299: 1271–7.
21.
ChatterjeeK, RouleauJA, ParmleyWW. Medical management of patients with angina. Has first-line management changed?JAMA1984; 252: 1170–6.
22.
DaleJ, LandmarkKH, MyhreE. The effects of nifedipine, a calcium antagonist, on platelet function.Am Heart J1983; 105: 103–5.
KlonerRA, BraunwaldE. Effects of calcium antagonists on infarcting myocardium.Am J Cardiol1987; 59: 84B–94B.
25.
HenryPD, ShuchleibR, BordaLJ, RobertsR, WilliamsonJR, SobelBE. Effects of nifedipine on myocardial perfusion and ischemic injury in dogs.Circ Res1978; 43: 372–80.
26.
ReimerKA, JenningsRB. Effects of calcium-channel blockers on myocardial preservation during experimental acute myocardial infarction.Am J Cardiol1985; 55: 107B–15B.
27.
KlonerRA, BraunwaldE. Observations on experimental myocardial ischaemia.Cardiovasc Res1980; 14: 371–95.
28.
WeintraubM. How to critically assess clinical drug trials.Drug Ther1982; 12: 13–23.
HutterAM, DesanctisRW, FlynnT, YeatmanLA. Nontransmural myocardial infarction: a comparison of hospital and late clinical course of patients with that of matched patients with transmural anterior and transmural inferior myocardial infarction.Am J Cardiol1981; 48: 595–602.
HollanderG, OzickH, GreengartA, ShaniJ, LichsteinE. High mortality, early reinfarction with first nontransmural myocardial infarction.Am Heart J1984; 108: 1412–6.
RobertsR. Recognition, diagnosis, and prognosis of early reinfarction: the role of calcium-channel blockers.Circulation1987; 75(suppl V): V139–47.
37.
NaylerWG, FerrariR, WilliamsA. Protective effect of pretreatment with verapamil, nifedipine, and propranolol on mitochondrial function in the ischemic and reperfused myocardium.Am J Cardiol1980; 46: 242–8.
38.
HenryPD, ShuchleibR, DavisJ, WeissES, SobelBE. Myocardial contracture and accumulation of mitochondrial calcium in ischemic rabbit heart.Am J Physiol1977; 233: H677–84.
ShenAC, JenningsRB. Myocardial calcium and magnesium in acute ischemic injury.Am J Pathol1972; 67: 417–40.
41.
BloomS, DavisDL. Calcium as mediator of isoproterenol-induced myocardial necrosis.Am J Pathol1972; 69: 459–70.
42.
BujaLM, WillersonJT. Infarct size—can it be measured or modified in humans?Prog Cardiovasc Dis1987; 29: 271–89.
43.
SobelBE, RobertsR, LarsonKB. Estimation of infarct size from serum MB creatine Phosphokinase activity: applications and limitations.Am J Cardiol1976; 37: 474–85.
44.
HackelDB, ReimerKA, IdekerRE. Comparison of enzymatic and anatomic estimates of myocardial infarct size in man.Circulation1984; 70: 824–35.
45.
VatnerSF, BaigH, MandersWT, MarokoPR. Effects of coronary artery reperfusion on myocardial infarct size calculated from creatine kinase.J Clin Invest1978; 61: 1048–56.
46.
HorieM, YasuH, OmoteS. A new approach for the enzymatic estimation of infarct size: serum peak creatine kinase and time to peak creatine kinase activity.Am J Cardiol1986; 57: 76–81.
47.
HearseDJ, GarlickPB, HumphreySM. The effect of drugs on enzyme release from the hypoxic myocardium.Eur J Cardiol1978; 7: 421–36.
48.
McphersonDD, HoracekBM, SpencerCA. Indirect measurement of infarct size—correlative variability of enzyme, radionuclear angiographic, and body surface map variables in 34 patients during the acute phase of first myocardial infarction.Chest1985; 88: 841–8.
49.
PolinerLR, BujaM, ParkeyRW. Comparison of different noninvasive methods of infarct sizing during experimental myocardial infarction.J Nucl Med1977; 18: 517–23.
50.
CreaF, DeanfieldJ, CreanP, SharomM, DaviesG, MaseriA. Effect of verapamil in preventing early postinfarction angina and reinfarction.Am J Cardiol1985; 55: 900–4.
51.
ThuesenL, JorgensenJJ, KvistgaardHJ. Effect of verapamil on enzyme release after early intravenous administration in acute myocardial infarction: double blind randomized trial.Br Med J1983; 286: 1107–8.
52.
BussmanW, SeherW, GruengrasM. Reduction of creatinine kinase and creatine kinase-MB indexes of infarct size by intravenous varapamil.Am J Cardiol1984; 54: 1224–30.
53.
The Danish Study Group on Verapamil in Myocardial Infarction.. Verapamil in acute myocardial infarction.Eur Hear J1984; 5: 516–28.
54.
MossAJ. Current status of calcium channel blocking drugs after myocardial infarction.Eur Heart J1986; 7(suppl A): 31–4.
55.
The Danish Study Group on Verapamil in Myocardial Infarction.The Danish Studies on verapamil in acute myocardial infarction.Br J Clin Pharmacol1986; 21: 1975–2045.
56.
MullerJE, MorrisonJ, StoneP. Nifedipine therapy for patients with threatened and acute myocardial infarction: a randomized, double-blind, placebo-controlled comparison.Circulation1984; 69: 740–7.
57.
HjalmarsonA, HerlitzJ, RydenL. Effect on mortality of metoprolol in acute myocardial infarction.Lancet1981; 2: 823–7.
SirnesPA, OverskeidK, PedersenTR. Evolution of infarct size during the early use of nifedipine in suspected acute myocardial infarction: the Norwegian Nifedipine Multicenter Trial.Circulation1984; 70: 638–44.
60.
WilcoxRG, HamptonJR, BanksDC. Trial of early nifedipine in acute myocardial infarction: the Trent Study.Br Med J1986; 293: 1204–8.
61.
BranaganJP, WalshK, KellyP, CollinsWC, MccaffertyD, WalshMJ. Effect of early treatment with nifedipine in suspected acute myocardial infarction.Eur Heart J1986; 7: 859–65.
62.
LoognaE, SylvenC, GrothT, MogensenL. Complexity of enzyme release during acute myocardial infarction in a controlled study with early nifedipine treatment.Eur Heart J1985; 6: 114–9.
63.
WalkerLJE, MackenzieG, AdgeyAA. Effect of nifedipine on enzymatically estimated infarct size in the early phase of acute myocardial infarction.Br Heart J1988; 59: 403–10.
64.
GottliebSO, BeckerLC, WeissJL. Nifedipine in acute myocardial infarction: an assessment of left ventricular function, infarct size, and infarct expansion.Br Heart J1988; 59: 411–8.
65.
ErbelR, PopT, MeinertzT. Combination of calcium channel blocker and thrombolytic therapy in acute myocardial infarction.Am Heart J1988; 115: 529–37.
66.
EisenbergPR, LeeRG, BielloDR, GeltmanEM, JaffeAS. Chest pain after nontransmural infarction: the absence of remediable coronary vasospasm.Am Heart J1985; 110: 515–21.
67.
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 J1988; 9: 354–64.
68.
MossAJ. Secondary prevention with calcium channel-blocking drugs in patients after myocardial infarction: a critical review.Circulation1987; 75(suppl V): V148–53.
69.
O'MAILIAJJ, SanderGE, GilesTD. Nifedipine-associated myocardial ischemia or infarction in the treatment of hypertensive urgencies.Ann Intern Med1987; 107: 185–6.
70.
BodenWE, KorrKS, BoughEW. Nifedipine-induced hypotension and myocardial ischemia in refractory angina pectoris.JA MA1985; 253: 1131–5.
71.
DeanfieldJ, WrightC, FoxK. Treatment of angina pectoris with nifedipine: importance of dose treatment.Br Med J1983; 286: 1467–70.
JariwallaAG, AndersonEG. Production of ischaemic cardiac pain by nifedipine.Br Med J1978; 1: 1181–2.
74.
ChiarielloM, GoldHK, LeinbachRD, DavisMA, MarokoPR. Comparison between the effects of nitroprusside and nitroglycerin on ischemic injury during acute myocardial infarction.Circulation1976; 54: 766–73.
75.
JudguttBI. Myocardial salvage by intravenous nitroglycerin in conscious dogs: loss of beneficial effect with marked nitroglycerin-induced hypotension.Circulation1983; 68: 673–84.
76.
NitzbergWD, NathHP, RogersWJ. Collateral flow in patients with acute myocardial infarction.Am J Cardiol1985; 56: 729–36.
77.
ZannadF, AmorM, KarcherG. Effect of diltiazem on myocardial infarct size estimated by enzyme release, serial thallium-201 single-photon emission computed tomography and radionuclide angiography.Am J Cardiol1988; 61: 1172–7.
78.
GibsonRS, BodenWE, TherouxP. Diltiazem and reinfarction in patients with non-Q-wave myocardial infarction.N Engl J Med1986; 315: 423–9.
79.
GibsonRS, YoungPM, BodenWE. Prognostic significance and beneficial effect of diltiazem on the incidence of early recurrent ischemia after non-Q-wave myocardial infarction: results from the Multicenter Diltiazem Reinfarction Study.Am J Cardiol1987; 60: 203–9.
80.
The Multicenter Diltiazem Postinfarction Trial Research Group.The effect of diltiazem on mortality and reinfarction after myocardial infarction.N Engl J Med1988; 319: 385–92.
81.
MossAJ, OakesD, BenhorinJ, MDPIT ResearchGroup. Effect of diltiazem on outcome in post-infarction patients with and without left ventricular dysfunction (abstract).Circulation1988; 78(suppl II): II-97.
