Amiodaron u usporedbi s drugim lijekovima za sprječavanje iznenadne srčane smrti
Abstract
Background
Sudden cardiac death (SCD) is one of the main causes of cardiac death. There are two main strategies to prevent it: managing cardiovascular risk factors and reducing the risk of ventricular arrhythmias. Implantable cardiac defibrillators (ICDs) constitute the standard therapy for both primary and secondary prevention; however, they are not widely available in settings with limited resources. The antiarrhythmic amiodarone has been proposed as an alternative to ICD.
Objectives
To evaluate the effectiveness of amiodarone for primary or secondary prevention in SCD compared with placebo or no intervention or any other antiarrhythmic drugs in participants at high risk (primary prevention) or who have recovered from a cardiac arrest or a syncope due to Ventricular Tachycardia/Ventricular Fibrillation, or VT/VF (secondary prevention).
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO) and LILACS on 26 March 2015. We reviewed reference lists of included studies and selected reviews on the topic, contacted authors of included studies, screened relevant meetings and searched in registers for ongoing trials. We applied no language restrictions.
Selection criteria
Randomised and quasi‐randomised trials assessing the efficacy of amiodarone versus placebo, no intervention, or other antiarrhythmics in adults. For primary prevention we considered participants at high risk for SCD. For secondary prevention we considered participants recovered from cardiac arrest or syncope due to ventricular arrhythmias.
Data collection and analysis
Two authors independently assessed the trials for inclusion and extracted relevant data. We contacted trial authors for missing data. We performed meta‐analyses using a random‐effects model. We calculated risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CIs). Three studies included more than one comparison.
Main results
We included 24 studies (9,997 participants). Eighteen studies evaluated amiodarone for primary prevention and six for secondary prevention. Only three studies used an ICD concomitantly with amiodarone for the comparison (all of them for secondary prevention).
For primary prevention, amiodarone compared to placebo or no intervention (17 studies, 8383 participants) reduced SCD (RR 0.76; 95% CI 0.66 to 0.88), cardiac mortality (RR 0.86; 95% CI 0.77 to 0.96) and all‐cause mortality (RR 0.88; 95% CI 0.78 to 1.00). The quality of the evidence was low.
Compared to other antiarrhythmics (three studies, 540 participants), amiodarone reduced SCD (RR 0.44; 95% CI 0.19 to 1.00), cardiac mortality (RR 0.41; 95% CI 0.20 to 0.86) and all‐cause mortality (RR 0.37; 95% CI 0.18 to 0.76). The quality of the evidence was moderate.
For secondary prevention, amiodarone compared to placebo or no intervention (two studies, 440 participants) appeared to increase the risk of SCD (RR 4.32; 95% CI 0.87 to 21.49) and all‐cause mortality (RR 3.05; 1.33 to 7.01). However, the quality of the evidence was very low. Compared to other antiarrhythmics (four studies, 839 participants) amiodarone appeared to increase the risk of SCD (RR 1.40; 95% CI 0.56 to 3.52; very low quality of evidence), but there was no effect in all‐cause mortality (RR 1.03; 95% CI 0.75 to 1.42; low quality evidence).
Amiodarone was associated with an increase in pulmonary and thyroid adverse events.
Authors' conclusions
There is low to moderate quality evidence that amiodarone reduces SCD, cardiac and all‐cause mortality when compared to placebo or no intervention for primary prevention, and its effects are superior to other antiarrhythmics.
It is uncertain if amiodarone reduces or increases SCD and mortality for secondary prevention because the quality of the evidence was very low.
PICO
Plain language summary
Amiodaron za sprječavanje iznenadne srčane smrti
Dosadašnje spoznaje
Iznenadna srčana smrt je u današnje vrijeme važan uzrok smrtnosti. Osobe u kojih postoje rizični čimbenici (srčana bolest) umiru neočekivano uslijed srčanih razloga, najčešće zbog aritmije (nepravilan rad srca). Liječenje izbora je ugradba uređaja za srčanu defibrilaciju (engl. implantable cardiac defibrillator, ICD), ali nije dostupan u zemljama niskog i srednjeg prihoda. Amiodaron je antiaritmijski lijek koji bi mogao smanjiti pojavnost ovog stanja i biti zamjena za ICD u uvjetima nedostupnosti.
Obilježja uključenih istraživanja
U ovom Cochrane sustavnom pregledu pretražili smo znanstvene baze kliničkih istraživanja usporedbe amiodarona i drugih antiaritmika s placebom u slučaju nenadane srčane smrti, smrtnosti i drugih nuspojava. Uključili smo odrasle osobe s rizičnim čimbenicima i podatkom o prethodnom iznenadnom srčanom zastoju (težak poremećaj srčanog rada koji uzrokuje aritmiju). Obuhvaćena su sva istraživanja dostupna do ožujka 2015.
Ključni rezultati
Našli smo 24 studije koje su obuhvatile 9.997 ispitanika. U ispitanika s visokim rizikom je nađen dokaz da amiodaron može spriječiti iznenadnu srčanu smrt ili smrtnost u usporedbi s placebom, te je vjerojatno učinkovitiji od ostalih antiaritmika.
U ispitanika koji su već preboljeli srčani zastoj, neizvjesno je da li amiodaron povećava ili smanjuje rizik novog događaja srčanog zastoja ili smrti.
Amiodaron može pogoršati nepovoljne učinke na štitnjaču ili pluća u usporedbi s placebom ili drugim antiaritmicima.
Kvaliteta dokaza
Cjelokupna kvaliteta dokaza u pronađenim studijama bila je niska.
