Superiority of combined diltiazem and propranolol therapy for angina pectoris.

Strauss, William; Parisi, Alfred F.

doi:10.1161/01.cir.71.5.951

Cited by 57 publications

(12 citation statements)

References 19 publications

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“…Moreover, examination of the relationship between ST segment depression and rate-pressure product, illustrated in figure 4, indicated that for any given rate-pressure product, diltiazem produced less electrocardiographic ischemia than placebo. This observation is consonant with previously published reports of diminished exercise-induced ST segment depression with lowdose (120 mg/day)37 and high-dose (360 mg/day)20 21 diltiazem.…”

Section: Resultssupporting

confidence: 92%

Beneficial effects of high-dose diltiazem in patients with persistent effort angina on beta-blockers and nitrates: a randomized, double-blind, placebo-controlled cross-over study.

Boden¹,

Bough²,

Reichman³

et al. 1985

Circulation

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The effects of orally administered diltiazem combined with maximally tolerated doses of /3-blockers and nitrates were assessed in 12 patients, who during stress testing exhibited persistent effort angina and continued objective evidence for inducible myocardial ischemia. Patients performed multistage semisupine exercise on a bicycle ergometer during equilibrium-gated radionuclide angiography after consecutive 2 week treatment periods of placebo or diltiazem 90 mg qid (mean dose 340 mg/day) combined with maximally tolerated propranolol (mean dose 178 mg/day) and isosorbide dinitrate (mean dose 137 mg/day). All medications (including diltiazem or placebo) were administered four times daily for the duration of the study. Diltiazem or placebo was administered according to a double-blind design, with randomized cross-over at the end of each 2 week treatment period. The average number of angina attacks decreased during the double-blind cross-over phase of the trial (7 + 7 episodes/week at baseline vs 4 ± 3 on placebo vs 2 ± 2 on diltiazem; p = .08). Angina pectoris was abolished during peak exercise in eight of 12 patients on diltiazem (p < .05 vs placebo). Diltiazem increased total exercise duration from 276 ± 92 to 310 ± 78 sec (p < .005 vs baseline). Diltiazem likewise increased the time to onset of angina from 231 ± 84 sec at baseline to 305 ± 77 sec (p < .005), as well as the time to the onset of 1 mm ischemic ST segment depression (p = .0 1). Diltiazem decreased heart rate at rest, during submaximal workload, and at peak exercise (p < .05), and decreased systolic blood pressure at peak exercise only (p < .05). A significant decline in rate-pressure product at submaximal and peak exercise was noted (p < .05). At any given workload there was significantly less ST segment depression during submaximal (p = .05) and peak exercise (p < .025). No difference was noted in mean left ventricular ejection fraction during placebo or diltiazem therapy at rest and during peak exercise. The effect of adding high-dose diltiazem to maximally tolerated doses of isosorbide and propranolol in improving exercise tolerance and reducing maximal ST segment depression suggests an attenuation of myocardial ischemia. A reduction in rate-pressure product at submaximal and peak workload indicates that patients can perform a higher degree of external work before the onset of ischemia. Thus the principal mechanism for the observed improvement in myocardial ischemia with diltiazem in patients with persistent effort angina in spite of maximally tolerated doses of ,Bblockers and nitrates appears to be a further incremental decrease in myocardial oxygen demand, although the decrease in heart rate may have facilitated an improvement in myocardial oxygen supply. Circulation 71, No. 6, 1197-1205, 1985

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Section: Resultssupporting

confidence: 92%

Beneficial effects of high-dose diltiazem in patients with persistent effort angina on beta-blockers and nitrates: a randomized, double-blind, placebo-controlled cross-over study.

Boden¹,

Bough²,

Reichman³

et al. 1985

Circulation

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“…Strauss and Parisi showed that a combination ofpropranolol and diltiazem significantly improved exercise duration in 24 patients with chronic, stable effort angina, when compared to propranolol or propranolol and placebo [62]. There was also an improvement in the rate of angina attacks.…”

Section: Chronic Stable Anginamentioning

confidence: 97%

Calcium channel antagonism and beta blockade in combination—A therapeutic alternative in cardiovascular disorders. A review

Lessem

Singh

1989

Cardiovasc Drug Ther

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Calcium-channel antagonists and beta-adrenergic blocking agents have become important modalities in the cardiovascular therapeutic armamentarium. These drugs are often administered as monotherapy to a wide range of cardiological patients with angina pectoris, hypertension, arrhythmias, congestive heart failure, and other diseases. Since within each class these drugs exhibit pharmacologic differences, it follows that their effectiveness varies in different disease states and that they exhibit a wide variety of side effects. In an attempt to optimize therapy, the individual drugs from these two classes can be combined; and the efficaciousness and side-effect profile of various combinations between calcium-channel antagonists and beta blockers are discussed in this review. Recommendations as to which patients may benefit from a combination and as to which patients may be harmed by the combination therapy will be made. Very few studies have compared the safety and efficacy of a single agent with the combination and with placebo in a controlled randomized fashion. To determine which therapy is superior and to determine which combination one should recommend under what circumstances, such placebo-controlled, randomized trials are a necessity, and will hopefully be performed although the complexity is enormous.

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“…Studies have shown that verapamil and diltiazem are as effective in preventing angina and improving exercise tolerance as BBs [51–54]. The combination of BBs and CCBs may be somewhat more effective than either alone, however this effect does not appear to be additive [55–57]. The combination of non-dihydropyridines with BBs is more effective, however is associated with a higher risk of adverse effects like bradycardia, palpitations, syncope, and gastrointestinal intolerance [55, 58].…”

Section: Management Of Anginamentioning

confidence: 99%

Advancements in pharmacotherapy for angina

Jain

Elgendy

Al‐Ani

et al. 2017

Expert Opinion on Pharmacotherapy

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Introduction Angina pectoris is the most prevalent symptomatic manifestation of ischemic heart disease, frequently leads to a poor quality of life, and is a major cause of medical resource consumption. Since the early descriptions of nitrite and nitrate in the 19th century, there has been considerable advancement in the pharmacologic management of angina. Areas covered Management of chronic angina is often challenging for clinicians. Despite introduction of several pharmacological agents in last few decades, a significant proportion of patients continue to experience symptoms (i.e., refractory angina) with subsequent disability. For the purpose of this review, we searched PubMed and Cochrane databases from inception to August 2016 for the most clinically relevant publications that guide current practice in angina therapy and its development. In this article, we briefly review the pathophysiology of angina and mechanism-based classification of current therapy. This is followed by evidence-based insight into the traditional and novel pharmacotherapeutic agents, highlighting their clinical usefulness. Expert opinion Considering the wide array of available therapies with different mechanism efficacy and limiting factors, a personalized approach is essential, particularly for patients with refractory angina. Ongoing research with novel pharmacologic modalities is likely to provide new options for management of angina.

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Superiority of combined diltiazem and propranolol therapy for angina pectoris.

Cited by 57 publications

References 19 publications

Beneficial effects of high-dose diltiazem in patients with persistent effort angina on beta-blockers and nitrates: a randomized, double-blind, placebo-controlled cross-over study.

Beneficial effects of high-dose diltiazem in patients with persistent effort angina on beta-blockers and nitrates: a randomized, double-blind, placebo-controlled cross-over study.

Calcium channel antagonism and beta blockade in combination—A therapeutic alternative in cardiovascular disorders. A review

Advancements in pharmacotherapy for angina

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