Anti-anginal drugs–beliefs and evidence: systematic review covering 50 years of medical treatment

Author:

Ferrari Roberto12,Pavasini Rita12,Camici Paolo G3,Crea Filippo4,Danchin Nicolas5,Pinto Fausto6,Manolis Athanasios7,Marzilli Mario89,Rosano Giuseppe M C10,Lopez-Sendon José11,Fox Kim12

Affiliation:

1. Cardiology Centre, University of Ferrara, Via Aldo Moro 8, Cona, Ferrara, Italy

2. Maria Cecilia Hospital, GVM Care & Research, Via Corriera 1, Cotignola, Ravenna, Italy

3. Vita Salute University and San Raffaele Hospital, Via Olgettina Milano, 58-60, Milano, Italy

4. Department of Cardiovascular and Thoracic Sciences, Catholic University, Largo Francesco Vito, 1, Roma, Italy

5. Cardiology, European Hospital Georges-Pompidiou, 20 Rue Leblanc, Paris, France

6. Lisbon University, Faculty of Medicine, Lisbon, Portugal

7. Department of Cardiology, Asklepeion General Hospital, 1 Vas. Pavlou Street, Voula Athens, Greece

8. Cardiothoracic Department, Lugarno Antonio Pacinotti, 43, Pisa, Italy

9. Nottola Cardiology Division, Località Nottola, Ospedali Riuniti Valdichiana Sudest, Siena, Italy

10. Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy

11. Cardiology Department, Hospital Universitario La Paz. IdiPaz, Universidad Autóonoma de Madrid, Paseo de la Castellana 261, 28036 Madrid, Spain

12. National Heart and Lung Institute, Imperial College and Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK

Abstract

Abstract Chronic stable angina is the most prevalent symptom of ischaemic heart disease and its management is a priority. Current guidelines recommend pharmacological therapy with drugs classified as being first line (beta blockers, calcium channel blockers, short acting nitrates) or second line (long-acting nitrates, ivabradine, nicorandil, ranolazine, and trimetazidine). Second line drugs are indicated for patients who have contraindications to first line agents, do not tolerate them or remain symptomatic. Evidence that one drug is superior to another has been questioned. Between January and March 2018, we performed a systematic review of articles written in English over the past 50 years English-written articles in Medline and Embase following preferred reporting items and the Cochrane collaboration approach. We included double blind randomized studies comparing parallel groups on treatment of angina in patients with stable coronary artery disease, with a sample size of, at least, 100 patients (50 patients per group), with a minimum follow-up of 1 week and an outcome measured on exercise testing, duration of exercise being the preferred outcome. Thirteen studies fulfilled our criteria. Nine studies involved between 100 and 300 patients, (2818 in total) and a further four enrolled greater than 300 patients. Evidence of equivalence was demonstrated for the use of beta-blockers (atenolol), calcium antagonists (amlodipine, nifedipine), and channel inhibitor (ivabradine) in three of these studies. Taken all together, in none of the studies was there evidence that one drug was superior to another in the treatment of angina or to prolong total exercise duration. There is a paucity of data comparing the efficacy of anti-anginal agents. The little available evidence shows that no anti-anginal drug is superior to another and equivalence has been shown only for three classes of drugs. Guidelines draw conclusions not from evidence but from clinical beliefs.

Funder

University of Ferrara

Fondazione Anna Maria Sechi per il Cuore

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

Reference27 articles.

1. On the use of nitrite of amyl in angina pectoris;Lauder Brunton;Lancet,1867

2. Nitroglycerine as a remedy for angina pectoris;Murrell;Lancet,1879

3. Double-blind trial of propranolol (Inderal) in angina of effort;Srivastava;Br Med J,1964

4. Iproveratril: experimental data on coronary dilatation and antiarrhythmic action;Melville;Can Med Assoc J,1964

5. History of calcium antagonists;Fleckenstein;Circ Res,1983

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