Heart failure occurs when the lower muscular heart chamber is unable to fill or eject blood normally due to heart disease of any origin. Acute heart failure syndromes (AHFS) are defined as gradual or rapid (over a period of less than 48 hours) deterioration in heart failure signs and symptoms resulting in a need for urgent therapy. There are many types of drugs and non-drug based interventions used for the treatment of AHFS. The aim of this review has been to determine the effectiveness and safety of nitrates (one drug group used for the treatment of AHFS) compared with alternative interventions in the treatment of patients with AHFS.
The four studies in this review included 634 patients with AHFS and employed two types of nitrates (isosorbide dinitrate and nitroglycerin). The studies compared nitrates with frusemide and morphine, frusemide alone, hydralazine, prenalterol, intravenous nesiritide and placebo. The study population in the trials was predominantly male (469/634 or 74% of all the patients included in the studies were male). The findings of this review indicate that there is no significant difference between nitrates and alternative treatment interventions for patients with AHFS in terms of healthcare outcomes. Nitrates appeared to be well tolerated in all four studies. Headaches is the most common side effect reported by patients. Headaches occurred more frequently when compared with nesiritide. There appeared to be no significant difference in the occurrence of symptomatic hypotension, pain, nausea and angina between patients administered nitroglycerin and nesiritide. The included studies did not report healthcare costs as an outcome measure.
The limitations of the review include the following: there were few studies eligible for inclusion (only four); the quality of the studies were relatively poor; the study participants were predominantly male; and all the eligible studies were conducted in developed Western countries. Consequently, the findings may not be generalisable to other healthcare settings and to females. The review also found no consistent evidence to support a difference in AHFS patients receiving nitrates or alternative interventions with regard to many of the healthcare outcome measures studied. Due to these limitations, the results of the review preclude definitive conclusions regarding the effectiveness and safety of nitrates compared with alternative interventions in the treatment of patients with AHFS.
There appears to be no significant difference between nitrate vasodilator therapy and alternative interventions in the treatment of AHFS, with regard to symptom relief and haemodynamic variables. Nitrates may be associated with a lower incidence of adverse effects after three hours compared with placebo. However, there is a lack of data to draw any firm conclusions concerning the use of nitrates in AHFS because current evidence is based on few low-quality studies.
Current drug therapy for acute heart failure syndromes (AHFS) consists mainly of diuretics supplemented by vasodilators or inotropes. Nitrates have been used as vasodilators in AHFS for many years and have been shown to improve some aspects of AHFS in some small studies. The aim of this review was to determine the clinical efficacy and safety of nitrate vasodilators in AHFS.
To quantify the effect of different nitrate preparations (isosorbide dinitrate and nitroglycerin) and the effect of route of administration of nitrates on clinical outcome, and to evaluate the safety and tolerability of nitrates in the management of AHFS.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (1950 to July week 2 2011) and EMBASE (1980 to week 28 2011). We searched the Current Controlled Trials MetaRegister of Clinical Trials (compiled by Current Science) (July 2011). We checked the reference lists of trials and contacted trial authors. We imposed no language restriction.
Randomised controlled trials comparing nitrates (isosorbide dinitrate and nitroglycerin) with alternative interventions (frusemide and morphine, frusemide alone, hydralazine, prenalterol, intravenous nesiritide and placebo) in the management of AHFS in adults aged 18 and over.
Two authors independently performed data extraction. Two authors performed trial quality assessment. We used mean difference (MD), odds ratio (OR) and 95% confidence intervals (CI) to measure effect sizes. Two authors independently assessed and rated the methodological quality of each trial using the Cochrane Collaboration tool for assessing risk of bias.
Four studies (634 participants) met the inclusion criteria. Two of the included studies included only patients with AHFS following acute myocardial infarction (AMI); one study excluded patients with overt AMI; and one study included participants with AHFS with and without acute coronary syndromes.
Based on a single study, there was no significant difference in the rapidity of symptom relief between intravenous nitroglycerin/N-acetylcysteine and intravenous frusemide/morphine after 30 minutes (fixed-effect MD -0.30, 95% CI -0.65 to 0.05), 60 minutes (fixed-effect MD -0.20, 95% CI -0.65 to 0.25), three hours (fixed-effect MD 0.20, 95% CI -0.27 to 0.67) and 24 hours (fixed-effect MD 0.00, 95% CI -0.31 to 0.31). There is no evidence to support a difference in AHFS patients receiving intravenous nitrate vasodilator therapy or alternative interventions with regard to the following outcome measures: requirement for mechanical ventilation, systolic blood pressure (SBP) change after three hours and 24 hours, diastolic blood pressure (DBP) change after 30, 60 and 90 minutes, heart rate change at 30 minutes, 60 minutes, three hours and 24 hours, pulmonary artery occlusion pressure (PAOP) change after three hours and 18 hours, cardiac output (CO) change at 90 minutes and three hours and progression to myocardial infarction. There is a significantly higher incidence of adverse events after three hours with nitroglycerin compared with placebo (odds ratio 2.29, 95% CI 1.26 to 4.16) based on a single study. There was no consistent evidence to support a difference in AHFS patients receiving intravenous nitrate vasodilator therapy or alternative interventions with regard to the following secondary outcome measures: SBP change after 30 and 60 minutes, heart rate change after 90 minutes, and PAOP change after 90 minutes. None of the included studies reported healthcare costs as an outcome measure. There were no data reported by any of the studies relating to the acceptability of the treatment to the patients (patient satisfaction scores).
Overall there was a paucity of relevant quality data in the included studies. Assessment of overall risk of bias in these studies was limited as three of the studies did not give sufficient detail to allow assessment of potential risk of bias.