Should patients receiving a radial artery conduit have post-operative Calcium Channel blockers ?

October 23, 2006

October 23, 2006

Anish Patel, Sanjay Asopa, Specialist Registrars in Cardiothoracic Surgery (Wessex Cardiothoracic Unit)

Joel Dunning, Wessex Cardiothoracic Unit

In [patients undergoing coronary grafting], does receiving a [radial artery conduit] improve [radial artery patency]?

You are looking after a 45-year old bricklayer with severe triple vessel disease who underwent urgent CABG using bilateral internal mammary arteries and a radial artery graft. He has progressed well and is awaiting discharge. He was on no medication on admission and asks you why he needs to have 6 weeks of Diltiazem three times per day as prescribed by your consultant. You have some difficulty justifying this medication and thus resolve to look up the literature that night.

Medline1966 to Jan 2006.

[Exp coronary artery bypass/OR coronary bypass.mp/OR coronary art$ bypass.mp OR CABG.mp OR exp Thoracic surgery/]AND[exp Radial artery/ OR radial arter$.mp]AND[exp calcium channel blockers/OR calcium channel blocker$.mp/OR calcium antagonist$.mp/OR exp diltiazem/OR diltiazem.mp/OR exp amlodipine/OR amlodipine.mp OR exp nitrates/OR nitrate$.mp OR GTN.mp OR exp vasodilator agents/OR exp nitroglycerin/]

The search found 98 papers. Of these papers14 represented the best evidence to answer the clinical question. Of note we included only in-vivo and clinical studies.

Gaudino[2005] randomized 100 consecutive patients who had radial artery grafts to Diltiazem or no therapy. All patients were evaluated clinically and with TI201 myocardial scintography but no differences were found. In addition 83 underwent angiography. Patency was over 95% in both groups and there was no difference between the groups. 12 patients had assessment of the vasospastic response of the radial artery to serotonin. Diltiazem did not attenuate this response.

Gaudino[2001] also looked at the clinical and angiographic effects of chronic channel blocker therapy continued beyond the first year in those having radial artery grafts. 120 patients who had radial arteries with no evidence of radial artery dysfunction at 1 year were randomly assigned to continue therapy with diltiazem 120mg daily or suspend therapy. At 5 years there was no difference in angina recurrence(10% in both groups) radial territory ischaemia (~5% both groups) or angiographic patency(~95%) In the subgroup who underwent challenge with endovascular serotonin, the radial arteries underwent spastic contraction but there was again no significant difference between groups. Similar results were also published by this group in 1998 [Possati] and 2003[Possati].

Shapira compared the use of nitrates and calcium channel blockers in the prevention of radial artery spasm in a randomized trial. No differences in operative mortality or morbidity, long term patency, thallium stress testing, need for stenting, or myocardial infarction were found. In this American study the overall cost of treatment with diltiazem was much more expensive than with nitroglycerin ($16,340 v $1,096).

Sperti evaluated the response to serotonin of the radial artery graft, the IMA graft and native coronary arteries in patients who had CABG with a radial artery graft. 22 patients were not on any calcium channel blockers and 9 were on chronic diltiazem treatment. Their results showed no significant difference in the diameter of the radial artery in its basal state between groups and thus oral diltiazem did not prevent serotonin induced vasoconstriction of the radial artery grafts.

Acer followed 102 patients for 5 years who received a radial artery. All patients were started on diltiazem and converted to oral diltiazem 250 mg daily and oral aspirin 100 mg daily.50 patients had an angiogram. 64 radial grafts were studied and 83% were patent. Diltiazem had continued to be used in 27 and 23 were not on any treatment for various reasons. There were 8 graft failures in the CCB group and 4 in patients who had stopped CCBs.

Broadman performed a prospective review of 175 of 249 patients. 2 patients had perioperative myocardial infarction but neither was related to radial artery dysfunction. Sixty patients underwent post operative angiography between 1 day and 40 weeks. Of these 28 were on calcium blocker therapy. Patency rate of the radial arteries was 95.7% and there was no effect with Calcium blocker usage.

Possati[2003] followed up 90 patients who received a radial artery then an angiogram an average of 9 years post-operatively. All patients received Diltiazem for a year post-operatively but 51 patients stopped this medication for a variety of reasons after this. There was no difference in graft patency, which was still perfect in 88% of patients.

Cameron performed an angiogram 5 years post radial artery grafting in 50 patients. 37 of these patients received calcium channel blockers. The patency rate was high at 89% and no correlation with CCB usage was found.

Skubas randomized 30 patients receiving a radial artery. 10 had intravenous nitroglycerin, 10 had intravenous nicardipine and 10 had normal saline. An intraoperative flow probe assessed radial artery flow and then they measured the change in flow in response to a vasoconstrictor. The flow was similar for all groups and increased for all patients in response to a vasoconstrictor in response to a higher blood pressure. Thus no vasospasm was seen and a vasoconstrictor did not induce vasospasm.

Arena performed angiography on 32 patients 1 year after radial artery harvest. Patients were randomized to nifedipine or control. There were only 2 patients whose radial arteries were found not to be patent and the reasons for this occlusion was felt to be technical rather then due to CCBs.

In 2001 Kalus reviewed the literature for the use of Calcium channel blockers or nitrates for the prevention of vasospasm. They referenced 17 papers and summarized their findings in a descriptive fashion. They found only small RCTs, small cohort studies and in vitro studies, and concluded that all these studies consistently find no clinical benefits for calcium channel blockers.

Moran et al randomized 115 patients receiving radial arteries to Diltiazem 180mg per day for 1 year or no treatment. Angiography at 1 year showed no difference and there were no clinical differences in symptoms or complications at 30 months follow up.

Myers et al performed a survey of Canadian surgical centres. Of 27 responding centres, 25 centres routinely use calcium channel blockers and 12 use nitrates in addition to this.

While routine use of Calcium channel blockers and nitrates in order to reduce vasospasm is in widespread use, none of the clinical studies that we identified provided any evidence for their benefit. Furthermore one study demonstrated that a vasoconstrictor mediated increase in blood pressure actually increased blood flow in the radial artery, and a further study reported that serotonin induced vasospasm was not attenuated by CCBs in vivo.

All these studies are underpowered to exclude a benefit of vasodilators in improving graft patency in the medium term. However an RCT that sought to prove an increase of 5% in patency rates (which are already around 90% or more) with a power of 80% would have to recruit and perform medium term angiography on 948 patients.

1. Gaudino M, Luciani N, Nasso G, Salica A, Canosa C, Possati G.. Is postoperative calcium channel blocker therapy needed in patients with radial artery grafts?
2. Gaudino M, Glieca F, Luciani N, Alessandrini F, Possati G.. Clinical and angiographic effects of chronic calcium channel blocker therapy continued beyond first postoperative year in patients with radial artery grafts...
3. Shapira OM, Alkon JD, Macron DS, Keaney JF Jr, Vita JA, Aldea GS, Shemin RJ.. Nitroglycerin is preferable to diltiazem for prevention of coronary bypass conduit spasm.
4. Sperti G, Manasse E, Kol A, Canosa C, Grego S, Milici C, Schiavello R, Possati GF, Crea F, Maseri A.. Comparison of response to serotonin of radial artery grafts and internal mammary grafts to native coronary arteries and the effect of diltiazem.
5. Possati G, Gaudino M, Alessandrini F, Luciani N, Glieca F, Trani C, Cellini C, Canosa C, Di Sciascio G.. Midterm clinical and angiographic results of radial artery grafts used for myocardial revascularization.
6. Acar C, Ramsheyi A, Pagny JY, Jebara V, Barrier P, Fabiani JN, Deloche A, Guermonprez JL, Carpentier A.. The radial artery for coronary artery bypass grafting: clinical and angiographic results at five years.
7. Brodman RF, Frame R, Camacho M, Hu E, Chen A, Hollinger I.. Routine use of unilateral and bilateral radial arteries for coronary artery bypass graft surgery.
8. Myers MG, Fremes SE.. Prevention of radial artery graft spasm: a survey of Canadian surgical centres.
9. Possati G, Gaudino M,Prati F, Alessandrini F, Trani C, Glieca F, Mazzari MA, Luciani N, Schiavoni G.. Long-Term Results of the Radial Artery Used for Myocardial Revascularization.
10. Cameron J, Trivedi S,Stafford G,Bett N.. Five-year Angiographic Patency of Radial Artery Bypass Grafts.
11. Skubas N, Barner HB, Apostolidou I, Lappas G.. Phenylephrine to increase blood flow in the radial artery used as a coronary bypass conduit.
12. Arena G, Abbate M.. Is calcium antagonist administration necessary after aortocoronary bypass with the radial artery?
13. Kalus JS, Lober CA.. Calcium-channel antagonists and nitrates in coronary artery bypass patients receiving radial artery grafts.
14. Moran SV, Baeza R, Guarda E, Zalaquett R, Irarrazaval J, Marchant E, Deck C.. Predictors of Radial Artery Patency for Coronary Bypass Operations.