August 15th 2017


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    Till the COURAGE trial was published , it had remained unclear whether initial treatment with percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) was superior to OMT alone. Patients with retrosternal pain on effort that disappeared by stopping or taking nitrates were considered to have stable angina (SA). The patients had to have at least 70% stenosis in one proximal coronary artery and objective evidence of myocardial ischemia (substantial ST segment depression or T wave inversion on the resting ECG or inducible ischemia with either exercise or pharmacologic vasodilator stress). Or the patients needed to have at least 80% block and classic angina without provocative testing. All patients were provided aspirin 81 to 325 mg per day or 75 mg of clopidogrel per day if there was aspirin intolerance. Medical ant ischemic treatment in both groups included long acting metoprolol, amlodipine, and isosorbide dinitrate along with lisinopril or losartan for secondary prevention. Simvastatin was given to lower low-density lipoproteins to 60 -85 mg%. Successful PCI was defined as normal coronary artery flow and less than 50% stenosis after balloon angioplasty and less than 20% stenosis post stent implantation. However very few patients received drug-eluting stents (DES).


    The researchers concluded that as an initial management strategy PCI added to OMR did not reduce the primary composite end point of death and myocardial infarction (MI) as compared with OMT during follow up of 2.5 to 7 years. The degree of angina relief was significantly greater with PCI. Limitations of the study include the preponderance of male patients (85%), 86% of patients were white, and almost all patients got DES. The COURAGE trial was a randomized study involving 2287 patients  of stable angina.


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    A sub study using stress myocardial perfusion single photon emission computed tomography (MPS), which measures extents of myocardial ischemia to risk stratify were subsequently published. The sub study included 314 patients and ischemia was assessed before and after therapy in these patients. Ischemia greater than 10% of left ventricular myocardium was considered moderate to severe ischemia. The authors concluded that in COURAGE patients who underwent serial MPS adding PCI to OMT resulted in greater reduction in ischemia compared with OMT alone. Patients with ischemia reduction had lower unadjusted risk for death or MI, particularly if baseline ischemia was 10% or more. Death or MI ranged from 0% to 39% for patients with no residual ischemia to more than 10% residual ischemia on follow up. Reduction in residual ischemic myocardium was significantly greater with PCI +OMT than in the OMT alone group. In this subset of COURAGE patients addition of PCI to OMT resulted in more effective reduction of ischemia than OMT alone. The greater reduction in ischemic burden was associated with improvement in angina, less need for nitrates.


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    The FAME 2 trial compared PCI with the best OMT available in stable angina patients who had significant physiological stenosis assessed by a pressure wire. FFR guided PCI with DES plus OMT compared with the best available OMT resulted in significantly improved clinical outcomes. The rate of the primary endpoint was significantly lower in the PCI group than in the medical alone group (8% versus 19.5%). The reduction was driven by a lower rate of urgent revascularization in the PCI group (4% vs. 16%), with no significant difference in death or MI. The FAME 2 trial studied 1220 patients with stable angina. But the PCI patients did have significant reduction in rate of death or MI after the initial 7 days following randomization. Only patients with an FFR of 0.80 or less in at least one large epicardial artery were enrolled. Second generatio0n stents were used in FAME 2. The trial was stopped early in response to the higher rate of urgent revascularization in those randomized to medical therapy alone. It was also seen that after 7 days there was a significant 44% reduction in death or MI in the PCI group , and 79% significant reduction in need for urgent revascularization in the PCI group.The UK RIPCORD study and a French registry found that pressure wire assessment of stable angina patients changed management strategy to PCI in 25% of cases in the UK and nearly 50% in France. These data have compelled the Europeans to make FFR as a class 1a recommendation in guiding treatment plans.



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    However on the basis of current evidence PCI is indicated only for symptomatic relief. Multiple randomized trials have not found reduction in mortality or MI with PCI compared with medical management alone. Quite a few trials did show better angina relief with PCI. The trials however were underpowered to detect difference in death; there were high conversion rates (cross-over) from medical therapy to PCI, outdated PCI techniques, and patients representing only 10% of real life patients. The trials were also unblinded. Also a high proportion of patients in old trials had minimal myocardial ischemia. European guidelines recommend revascularization to patients with evidence of ischemia in >10% of the left ventricle. Implantation of DES results in less than 5% restenosis and less than 1% stent thrombosis.


    Optimal medical therapy may be enough initially in stable angina. Aspirin is preferred because it reduces mortality. Clopidogrel may be used in those with coexistent peripheral vascular disease, or in those who cannot tolerate aspirin. No data are available to support use of ticagrelor and prasugrel in stable angina. Statins are used to cut down cardiovascular rates. Angiotensin converting enzyme inhibitors are used when LV ejection fraction is 40% or less, in diabetics, in CKD, hypertension or previous MI as they reduce mortality, MI, stroke and heart failure. Beta blockers or calcium channel blockers are first line anti angina drugs. If these are not effective or not tolerated consider using nitrates, nicorandil, ivabradine or ranolazine.


    To conclude, PCI is an excellent choice to provide relief from symptoms of angina, while recent trials suggest PCI would be the treatment of choice for patients of stable angina with 10% myocardial ischemia or an FFR of less than 0.80. So if you come across a 56 year-old clerk with well controlled on a beta-blocker what would you advise him? The best advice would be a non- invasive nuclear test to find out the extent of ischemia. In case more than 10% of the left ventricle is at peril PCI should be offered. On the other hand if a patient has little ischemia but a whole lot of chest discomfort then also PCI would be the best alternative. It would be prudent to keep in mind there may be no pain in the elderly, in women, in diabetics and also in some patients with hypertension. There is always the chance of coming across patients with severe coronary disease who somehow fail to recognize the ramifications or lethality of their symptoms.