Abstract
Non-pharmacological strategies for secondary prevention-regular physical activity, yoga, heart-healthy diet, tobacco and smoking cessation, and maintenance of optimal weight are of proven value; although adherence to them is very low.
The pharmacological interventions—antiplatelet drugs, statin therapy, appropriate use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, target-oriented glycemic control are conventional and proven methods for secondary prevention. Reducing the residual cardiovascular risk (RCR) is an emerging idea in secondary CVD prevention. RCR has three main components (Table 1)—metabolic, inflammatory, and thrombotic factors. 1
The Three Components of Residual Cardiovascular Risk.
Triglyceride and Lipoprotein-(a) lowering, use of anti-inflammatory agents, and newer anticoagulants in low doses are the new suggestions for reducing the residual risk. The recently published and widely discussed guidelines on—chronic coronary disease and secondary prevention focused on the use of SGLT2 inhibitors and GLP1 agonists in select groups, the rationale use of beta-blockers, adjunctive anti-lipid agents [ezetimibe, bempedoic acid-] and shorter DAPT in patients with high bleeding risk. The recent guidelines negated the use of non-prescription or dietary supplements like fish oils, omega-3 fatty acids, and vitamins.
Another molecule that is making ripples is Icosapent ethyl which can address the metabolic risk. By its effective role in the reduction of triglycerides (especially in the diabetic population) and atheroprotective effects, it could show positive CV outcomes and reduction of CV events in hypertriglyceridemia patients (REDUCE-IT) and in those with established ASCVD (REDUCE prior MI/PCI/CABG trials). Professional bodies like the European Society of Cardiology, ADA and AACE, and AHA made favorable recommendations for its use in secondary prevention. It has to be used as 4 Gm./day in patients with high ASCVD risk while continuing the statins with a target of less than 135 mg/dL for triglycerides. The additional expense and the need to consume four big capsules in a day may be a limitation for its adaption in our clinical practice. 2
It is interesting to see the ezetimibe and bempedoic acid percolating into our daily practice of lipid management in addition to the optimal use of statins. We are not far away from the use of Inclisiran or PCSK9 inhibitor periodic injections in daily practice more like preventive vaccinations, when apparently healthy. Lipoprotein-(a) reduction was strongly advocated by Enas, way back in the mid-90s, when he asked South Asians to take Niacin 50 mg of daily as prevention from malignant CAD. But none of the professional bodies like AHA, ADA, and ESC endorsed his viewpoint. Lipoprotein-(a) came into limelight only in the recent past as a preventive strategy to address the RCR.3, 4 AKCEA-APO (a)-LRX study published in 2020, had proven the effectiveness of a hepatocyte-directed antisense oligonucleotide-AKCEA-APO (a)-LRx, for Lipoprotein-(a) reduction. In the absence of any existing effective therapies for elevated lipoprotein-(a) this trial gave a new hope. 5
The inflammatory hypothesis supports the long-term use of cytokine-based therapy to prevent cardiovascular events in patients with established CAD. Canakinumab, an inhibitor of IL-1 beta was studied in the CANTOS trial, which showed a significant reduction in cardiovascular events compared to placebo. This was a big initial step to move toward controlling inflammation as a strategy for secondary prevention. The anti-gout agent colchicine found an important mention in AHA/ACC/ACCP/ASPC/NLA/PCNA guideline (2023) for the management of patients with chronic coronary disease. These guidelines endorse colchicine as a secondary prevention [COR: 2b; LOE: B-R]. 6 In this issue of IJCC, Dr. Kartik Jadav has vividly reviewed the new evidence for the emerging role of this age-old anti-inflammatory agent in various stages of coronary artery disease. He brought out the current perspective on this molecule which looks to have great potential in future medical practice. 7
Another debatable issue is whether it is rational to use newer oral anticoagulants (NOACs) in low doses in the setting of secondary prevention? The 2020 ESC guidelines recommended the use of one week of triple antithrombotic therapy followed by dual therapy (DOAC plus Clopidogrel) until one year after which NOAC monotherapy may suffice. 8 In the COMPASS trial, a combination of low-dose rivaroxaban (2.5 mg) and aspirin proved to be an effective strategy for the prevention of major events like strokes, MI, and death in stable patients. 9 It is heartening to see such development of novel strategies for the management and prevention of CV diseases in the near future.
