Background

Coronary angiogram has been identified as the current gold standard for assessing the coronary arteries to evaluate the level of disease present in patients with suspected coronary artery disease.1 Coronary angiography is the diagnostic procedure utilized to view and evaluate the level of disease in the coronary arteries, whereas angioplasty is the term used for the interventional procedure to improve the passage of blood flow through the coronary arteries.2 These procedures can be carried out percutaneously via the femoral, brachial or radial arteries, with the femoral approach being the traditional option.2 The femoral artery presents a large access point to carry out coronary procedures, with the extent of access to the coronary arteries depending on the level of peripheral vascular disease of the patient. Carrying out coronary procedures via the femoral artery requires the patient to lie flat throughout the procedure and to continue doing so for up to 3.5 hours in the recovery period. During this period, patients can experience back pain as a result of lying flat for an extended period of time.3 Other complications associated with the femoral route include bleeding, hematoma, pseudoaneurysm, nerve damage, arteriovenous fistula, stroke and death.2

Given the disadvantages of the femoral approach, other methods to perform percutaneous coronary procedures have been developed. The transradial approach (TRA) for percutaneous coronary procedures was first documented in 1989 by Campeau, initially for angiography.4 Campeau4 identified that the absence of significant veins and nerves presented a valuable option as it further reduced the possibility of complications such as nerve damage or injury and arteriovenous fistulas. Gaining access through the radial artery for coronary angiography or angioplasty offered an access point that was more easily compressed resulting in hemostasis once the sheath was removed. This approach was further developed by Kiemeneij, who carried out the first interventional case in 1992.2 The use of the TRA in coronary procedures has since increased in popularity with an increase in uptake globally. This increase in popularity can be attributed to the decrease of vascular complications, faster post-procedural ambulation times for patients, increase in patient satisfaction, reduced cost and decreased mortality.5-8 The TRA has been identified as significantly reducing local vascular complications from 2.8% in femoral approach to 0.3% via the TRA.9 Entry site complications, including major hematoma, vascular surgery and arteriovenous fistula, have a documented drop from 0.42 to 0.09, respectively, when comparing the femoral approach with the TRA.9

Despite the benefits associated with the TRA, access failure remains a concern for proceduralists. Radial artery spasm (RAS) occurs in up to 34% of cases and has been identified as a major cause of access failure and considerable pain to the patient during the procedure. Radial artery spasm can significantly reduce the ability of the proceduralist to manipulate the guide wire or catheter, resulting in the need to abandon the procedure from the radial artery access point and reattempt the procedure via the femoral artery. This results in an increase in procedural times, exposure to radiation and cost.10,11 The radial artery has a higher sensitivity to spasm in comparison with the femoral artery, which is reflected in the classification of the radial artery as a type III (limb) artery.12 Radial artery spasm can be caused by the circulating catecholamines stimulating the alpha I adrenoreceptors, which in turn contract smooth muscle cells of the radial artery.10 Other causes attributed to RAS can include mechanical stimulants, such as catheter and guide wire manipulation.13 Kristic and Lukenda10 identify that RAS has the potential to lead to radial artery injury or more severe radial artery occlusion.

To overcome RAS, the administration of various intra-arterial and intravenous medications including calcium channel blockers5,8,14-18,19 and nitrates14,20 as a premedication has been used with varying effects.21 Calcium channel blockers, such as verapamil and diltiazem, reduce the influx of calcium into vascular and arterial smooth muscle resulting in vasodilatory effects, while nitrates, such as isosorbide dinitrate and nitroglycerin, relax smooth muscle resulting in vasodilation. Despite the vasodilating effects of calcium channel blockers and nitrate medications, they have varying effects on RAS. One study demonstrated a significant reduction in the incidence of RAS among patients receiving 5 mg of calcium channel blockers compared with those who received placebo.17 In contrast, another study undertaken on 591 patients demonstrated no significant difference in the incidence of RAS among those who received various types of calcium channel blockers.8 Nitrates are reported to have been used extensively in the reduction of RAS.14,20 However, there is contradictory evidence relating to the use of nitrates to prevent RAS, with some studies reporting beneficial effects14 and others reporting no difference.20 Similarly, a combination of nitrates and calcium channel blockers demonstrate mixed results and while most experts agree upon the need for the prophylactic use of medication to reduce the occurrence of RAS, operators in Japan have carried out TRA coronary catheterization without spasm prophylaxis.8 Currently, there is insufficient evidence to support a specific pharmacological medication as well as the optimal dose of the medication to reduce the rates of RAS. The aim of the review is to systematically assess the literature to investigate the effectiveness of vasodilating medications on RAS in patients having coronary procedures. A preliminary search identified no existing or registered systematic reviews on this topic.

Inclusion criteria

Types of participants

The current review will consider studies that include participants aged 18 years and over undergoing non-emergent transradial percutaneous coronary artery procedures.

Types of intervention(s)/phenomena of interest

The current review will consider studies that use vasodilating intravenous and intra-arterial medications (such as nitrates, calcium channel blockers etc.) or combinations of these medications prior to commencing and during transradial coronary approaches to reduce RAS. Varying doses of vasodilating medications that are administered via the intravenous or intra-arterial route will be considered for this review. Specific comparisons will be made between:

* intravenous and/or intra-arterial vasodilating medication compared with no treatment,

* intravenous and/or intra-arterial vasodilating medication compared with placebo, and

* different types of intravenous and intra-arterial vasodilating medications.

Outcomes

The current review will consider studies that include the following outcomes using objective and/or subjective measures:

* incidence of RAS as assessed by angiography or ultrasound or resistance felt by operator while manipulating the catheter,8,17

* pain associated with RAS, and

* side effects/adverse events of medication.

Types of studies

The current review will consider randomized controlled trials published in the English language.

Search strategy

The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of MEDLINE, CINAHL, EMBASE and Scopus will be undertaken followed by an analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search, using all identified keywords and index terms, will then be undertaken across all included databases mentioned below. The key terms used will be transradial coronary procedures, coronary angio*, premedication, verapamil, nitroglycerin, phentolamine, nitroprusside, nicorandil, diltiazem, molsidomine, magnesium sulphate, vasodilator, artery spasm and radial, refer to Appendix I for details on how search terms will be combined. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Studies published in English will be considered for inclusion in this review. Studies published from 1989 to the present will be considered for inclusion in this review as prior to this date no transradial percutaneous studies had been published.10

The databases to be searched include: MEDLINE, CINAHL, Scopus, Embase, Cochrane Central, clinicaltrials.gov and ANZ register. The search for unpublished studies will include: Dissertation Abstracts International, ProQuest Dissertations & Theses and MedNar.

Assessment of methodological quality

Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix II). Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer.

Data extraction

Quantitative data will be extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix III). The data extracted will be carried out by one of the authors and checked by the second and will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. If there is information missing in relevant studies, the corresponding author will be contacted and given the opportunity to clarify the information.

Data synthesis

Quantitative data will, where possible, be pooled in statistical meta-analysis using Review Manager 5.3. All results will be subject to double data entry. Clinical heterogeneity will be assessed by considering the populations, interventions and outcomes between the studies. Statistical heterogeneity will be investigated by calculating the I² statistic, and if this indicates a high level of heterogeneity among the trials included in an analysis, a random effects meta-analysis will be preferred for the overall summary. Where high levels of heterogeneity are found, they will be explored by the prespecified subgroup analyses based on type of medication or method of RAS identification and by sensitivity analyses excluding the trials most susceptible to bias based on the quality assessment. Fixed effects meta-analysis will be used for combining study data if the trials are judged to be sufficiently similar. Relative risks and 95% confidence intervals (CIs) will be calculated for dichotomous data. Analysis of continuous data will be undertaken using the mean and standard deviation values to derive weighted mean differences and their 95% CIs. Where synthesis is inappropriate, a narrative overview will be undertaken.

Appendix I: Search strategy

Appendix II: Appraisal instruments

MAStARI appraisal instrument

Appendix III: Data extraction instruments

MAStARI data extraction instrument

References