Colchicine
Guidelines provide a weak recommendation that the anti-inflammatory agent colchicine may be considered for select patients with CCD who are at high-risk of subsequent events despite maximum tolerated guideline-directed management and therapy.[26]Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease: a report of the American Heart Association/American College of Cardiology joint committee on clinical practice guidelines. Circulation. 2023 Aug 29;148(9):e9-119.
https://www.ahajournals.org/doi/10.1161/CIR.0000000000001168
http://www.ncbi.nlm.nih.gov/pubmed/37471501?tool=bestpractice.com
Trials of long-term therapy (1 to 3 years) have shown reduction in a combined cardiovascular outcome with a trend toward reduced cardiovascular death counterbalanced by a trend toward increased noncardiovascular death.[234]Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020 Nov 5;383(19):1838-47.
https://www.nejm.org/doi/10.1056/NEJMoa2021372
http://www.ncbi.nlm.nih.gov/pubmed/32865380?tool=bestpractice.com
[235]Fiolet ATL, Opstal TSJ, Mosterd A, et al. Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials. Eur Heart J. 2021 Jul 21;42(28):2765-75.
https://academic.oup.com/eurheartj/article/42/28/2765/6188997
http://www.ncbi.nlm.nih.gov/pubmed/33769515?tool=bestpractice.com
Limitations include GI adverse effects (which prompted 10% withdrawal during the run in phase of the largest study) as well as a narrow therapeutic index, drug interactions, and the need for dose adjustments in renal impairment.[26]Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease: a report of the American Heart Association/American College of Cardiology joint committee on clinical practice guidelines. Circulation. 2023 Aug 29;148(9):e9-119.
https://www.ahajournals.org/doi/10.1161/CIR.0000000000001168
http://www.ncbi.nlm.nih.gov/pubmed/37471501?tool=bestpractice.com
[234]Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020 Nov 5;383(19):1838-47.
https://www.nejm.org/doi/10.1056/NEJMoa2021372
http://www.ncbi.nlm.nih.gov/pubmed/32865380?tool=bestpractice.com
Further studies are required to guide clinical practice.
Other antianginal therapies
Nicorandil and trimetazidine are antianginal agents that are not available in the US, but are used in other countries. The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK has issued warnings concerning advice on the use of nicorandil.[236]Medicines and Healthcare products Regulatory Agency. Nicorandil (Ikorel): now second-line treatment for angina - risk of ulcer complications. Jan 2016 [internet publication].
https://www.gov.uk/drug-safety-update/nicorandil-ikorel-now-second-line-treatment-for-angina-risk-of-ulcer-complications
There is limited evidence supporting the use of trimetazidine.[237]Danchin N, Marzilli M, Parkhomenko A, et al. Efficacy comparison of trimetazidine with therapeutic alternatives in stable angina pectoris: a network meta-analysis. Cardiology. 2011;120(2):59-72.
http://www.ncbi.nlm.nih.gov/pubmed/22122948?tool=bestpractice.com
[238]Ajabnoor A, Mukhtar A. Effect of trimetazidine on the functional capacity of ischemic heart disease patients not suitable for revascularization: meta-analysis of randomized controlled trials. PLoS One. 2022 Feb 11;17(2):e0263932.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263932
http://www.ncbi.nlm.nih.gov/pubmed/35148340?tool=bestpractice.com
Other LDL-lowering therapies
Bempedoic acid and inclisiran are newer nonstatin therapies approved for use with diet and maximally tolerated statin therapy in adults who require additional lowering of LDL-C.[239]Writing Committee, Lloyd-Jones DM, Morris PB, et al. 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022 Oct 4;80(14):1366-1418.
https://www.sciencedirect.com/science/article/pii/S0735109722055942?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/36031461?tool=bestpractice.com
They may be selectively considered for high risk patients with severely or persistently elevated LDL despite use of (or for those unable to use) better established alternatives. Trials assessing clinical outcomes are ongoing, with one trial showing benefit in statin-intolerant patients.[240]Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023 Apr 13;388(15):1353-64.
http://www.ncbi.nlm.nih.gov/pubmed/36876740?tool=bestpractice.com
[241]Nissen SE, Menon V, Nicholls SJ, et al. Bempedoic acid for primary prevention of cardiovascular events in statin-intolerant patients. JAMA. 2023 Jul 11;330(2):131-40.
https://jamanetwork.com/journals/jama/fullarticle/2806646
http://www.ncbi.nlm.nih.gov/pubmed/37354546?tool=bestpractice.com
[242]Nicholls SJ, Nelson AJ, Lincoff AM, et al. Impact of bempedoic acid on total cardiovascular events: a prespecified analysis of the CLEAR outcomes randomized clinical trial. JAMA Cardiol. 2024 Mar 1;9(3):245-53.
http://www.ncbi.nlm.nih.gov/pubmed/38231501?tool=bestpractice.com
Coronary-sinus-reducing device
A coronary-sinus-reducing device has shown some promise in the small COSIRA trial, improving symptoms and quality of life in patients with refractory angina who were not candidates for revascularization.[243]Verheye S, Jolicoeur EM, Behan MW, et al. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med. 2015 Feb 5;372(6):519-27.
https://www.nejm.org/doi/full/10.1056/NEJMoa1402556
http://www.ncbi.nlm.nih.gov/pubmed/25651246?tool=bestpractice.com