Trimetazidine for stable angina.
BACKGROUND
Patients with stable angina not controlled by monotherapy with nitrates, beta blockers, or calcium channel blockers are often treated with combinations of these drugs. There may be adverse effects from, or contraindications to, the use of combinations. In low risk groups, medical treatment appears to be as good an option as percutaneous transluminal coronary angioplasty in terms of averting myocardial infarction, death, or subsequent revascularization. Revascularization procedures are too costly or inaccessible for many patients in developing countries therefore effective and safe medical treatment is needed. Trimetazidine is a less well known anti-anginal drug that controls myocardial ischaemia through intracellular metabolic changes. Trimetazidine has been reported, in some studies, to be better tolerated than combined anti-anginal therapy; however it is not considered in published guidelines.


OBJECTIVE
To determine the efficacy and tolerability of trimetazidine in patients with stable angina.


METHODS
We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS and SCISEARCH, without language restriction, from inception to October 2003. Experts in the field were contacted to locate unpublished studies.


METHODS
Randomised studies comparing trimetazidine with placebo, or other anti-angina drug in adults with stable angina.


METHODS
Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted data.


RESULTS
Twenty-three studies (1378 patients) met the inclusion criteria. There was a paucity of information about mortality, cardiovascular events and quality of life. Trimetazidine, compared with placebo, reduced the number of weekly angina attacks ( mean difference -1.44, 95% CI -2.10 to -0.79; P < 0.0001), reduced weekly nitroglycerin tablet consumption (95% CI -1.47 to -2.20, -0.73; P < 0.0001) and improved exercise time to 1 mm segment depression (P=0.0002). Four small trials (263 patients) compared trimetazidine against other anti-anginal agents. One favoured trimetazidine over nitrates. Three tended to favour alternative regimens but with confidence intervals consistent with both major increases and decreases in frequency of angina episodes. In this subgroup, adverse events were considered in 5 trials (448 patients) and totals of 2 versus 12 drop outs due to adverse events were observed in the trimetazidine and alternative regimens respectively, but this was mostly driven by a single trial.


CONCLUSIONS
Trimetazidine is effective in the treatment of stable angina compared with placebo, alone or combined with conventional anti-anginal agents. Trimetazidine may result in fewer dropouts due to adverse events. Large, long term trials comparing trimetazidine with other anti-anginal drugs assessing clinically relevant important outcomes are required to establish its role in clinical management.
Ciapponi
A
A
Hospital Italiano de Buenos Aires, Division of Family and Preventive Medicine, Peron 4272, Buenos Aires, Argentina 1199. agustin.ciapponi@hospitalitaliano.org.ar
Pizarro
R
R
Harrison
J
J
D000328:Adult; D000787:Angina Pectoris / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D014292:Trimetazidine / Q000009:adverse effects / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D014665:Vasodilator Agents; D014292:Trimetazidine