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Dr. Peter Ong
Prof. Udo Sechtem,
In patients with ST-segment myocardial infarction (STEMI) primary percutaneous coronary intervention (PCI) of the culprit lesion is the treatment of choice [[i]]. However, it is known that approximately 50% of patients with STEMI have multivessel disease [[ii]] and it has been shown that such patients have a worse outcome compared to patients with single vessel disease [[iii]].
Several approaches of dealing with the remaining lesions are possible:one can perform PCI at the time of treating the culprit lesion based on the angiographic appearance of the stenoses:
This recommendation has been challenged by the PRAMI trial published in 2013 [[vii]]. In this multicenter study from the United Kingdom, 465 patients with STEMI were randomized in a 1:1 fashion to either multivessel PCI of all lesions >50% (preventive PCI) or culprit lesion only (no preventive PCI). There was a statistically significant benefit for patients with preventive PCI regarding the primary outcome (combination of composite of death from cardiac causes, nonfatal myocardial infarction, or refractory angina) and also for the components nonfatal MI and refractory angina with a strong tendency in favour of multivessel PCI for death of cardiac causes.
In addition, the secondary outcome, i.e. repeat revascularization, occurred significantly more often in the group without preventive PCI. In the CvLPRIT study [[viii]], a multicenter trial from the United Kingdom, 296 patients with STEMI were randomized in a 1:1 fashion to either culprit lesion only PCI or multivessel PCI of all stenoses >70%. Complete revascularization was associated with a statistically significant benefit for the primary endpoint (combination of all-cause death, recurrent myocardial infarction, heart failure and ischaemia-driven revascularization within 12 months). The main point of criticism is that no ischaemia testing was performed as an inpatient nor following discharge in the control group leaving potentially critical lesions untreated.
A different approach was chosen in the recently published DANAMI-3-PRIMULTI trial [[ix]]. In this Danish study 627 patients with STEMI and multivessel disease were randomized in a 1:1 fashion to either sole treatment of the culprit lesion with PCI or complete FFR-guided revascularization before discharge.Although no significant difference was found between the two groups for all-cause mortality and non-fatal reinfarction at a median of 27 months follow-up, patients in the FFR-guided revascularization group had significantly fewer repeat revascularizations.Again, patients in the control group (culprit lesion PCI only) were potentially undertreated because no ischaemia testing was performed after the initial intervention.The results of the studies addressed above have stimulated the discussion whether and when non-culprit lesions in patients with STEMI and multivessel disease should be treated.
In contrast to some authors who suggested that immediate multivessel PCI in such patients should be the default strategy, we strongly believe that all three studies (i.e. PRAMI, CvLPRIT, DANAMI-3-PRIMULTI) had a seriously flawed study design preventing meaningful conclusions regarding optimal treatment. The fault was that patients who received only PCI of the culprit lesion were not allowed to be treated according to the current guideline recommendation.
The guidelines  call for staged revascularization after stabilization of the patient according to proof of myocardial ischaemia on further testing. However, in all three studies the study protocol demanded that patients in the control groups were treated in a suboptimal fashion. This may have favoured that all three trials showed statistically significant differences between the culprit lesion only group and the multivessel PCI group for the various endpoints. The fact that the staged approach recommended by the guidelines can still be regarded as the treatment of choice is supported by recent data from Israel showing that patients with STEMI and multivessel disease who underwent myocardial scintigraphy after primary PCI of the culprit lesion and were found to have no relevant ischaemia had a similar prognosis compared to patients with STEMI and single vessel disease [[x]].
There are some other potential pitfalls of the unconditioned multivessel PCI approach.
Although several randomized studies have suggested a benefit for multivessel PCI in patients with STEMI and multivessel disease, none of the studies compared multivessel PCI with a staged PCI-approach according to the current guideline recommendations. Thus, we believe that culprit lesion only PCI and staged evaluation of remaining areas of myocardial ischaemia with subsequent PCI is still preferable in patients with STEMI and multivessel disease. This should, however, be proven in an appropriate randomized trial.
[i] Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Jüni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI).Eur Heart J. 2014;35:2541-619.
[ii] Goldstein JA, Demetriou D, Grines CL, Pica M, Shoukfeh M, O'Neill WW. Multiple complex coronary plaques in patients with acute myocardial infarction. N Engl J Med. 2000;343:915-22.
[iii] Sorajja P, Gersh BJ, Cox DA, McLaughlin MG, Zimetbaum P, Costantini C, Stuckey T, Tcheng JE, Mehran R, Lansky AJ, Grines CL, Stone GW. Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. Eur Heart J. 2007;28:1709-16.
[iv] Kornowski R, Mehran R, Dangas G, Nikolsky E, Assali A, Claessen BE, Gersh BJ, Wong SC, Witzenbichler B, Guagliumi G, Dudek D, Fahy M, Lansky AJ, Stone GW; HORIZONS-AMI Trial Investigators. Prognostic impact of staged versus "one-time" multivessel percutaneous intervention in acute myocardial infarction: analysis from the HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trial. J Am Coll Cardiol. 2011;58:704-11.
[v] Hannan EL, Samadashvili Z, Walford G, Holmes DR Jr, Jacobs AK, Stamato NJ, Venditti FJ, Sharma S, King SB 3rd. Culprit vessel percutaneous coronary intervention versus multivessel and staged percutaneous coronary intervention for ST-segment elevation myocardial infarction patients with multivessel disease. JACC Cardiovasc Interv. 2010;3:22-31.
[vi] Iqbal MB, Ilsley C, Kabir T, Smith R, Lane R, Mason M, Clifford P, Crake T, Firoozi S, Kalra S, Knight C, Lim P, Malik IS, Mathur A, Meier P, Rakhit RD, Redwood S, Whitbread M, Bromage D, Rathod K, MacCarthy P, Dalby M; London Heart Attack Centre (HAC) Group Investigators. Culprit vessel versus multivessel intervention at the time of primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction and multivessel disease: real-world analysis of 3984 patients in London. Circ Cardiovasc Qual Outcomes 2014;7:936-43.
[vii] Wald DS, Morris JK, Wald NJ, Chase AJ, Edwards RJ, Hughes LO, Berry C, Oldroyd KG; PRAMI Investigators.Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med. 2013;369:1115-23.
[viii] Gershlick AH, Khan JN, Kelly DJ, Greenwood JP, Sasikaran T, Curzen N, Blackman DJ, Dalby M, Fairbrother KL, Banya W, Wang D, Flather M, Hetherington SL, Kelion AD, Talwar S, Gunning M, Hall R, Swanton H, McCann GP. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial. J Am Coll Cardiol. 2015;65:963-72.
[ix] Engstrøm T, Kelbæk H, Helqvist S, Høfsten DE, Kløvgaard L, Holmvang L, Jørgensen E, Pedersen F, Saunamäki K, Clemmensen P, De Backer O, Ravkilde J, Tilsted HH, Villadsen AB, Aarøe J, Jensen SE, Raungaard B, Køber L; DANAMI-3—PRIMULTI Investigators. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial. Lancet. 2015;386:665-71.
[x] Weissler-Snir A, Gurevitz C, Assali A, Vaknin-Assa H, Bental T, Lador A, Yavin H, Perl L, Kornowski R, Lev E. Prognosis of STEMI Patients with Multi-Vessel Disease Undergoing Culprit-Only PCI without Significant Residual Ischemia on Non-Invasive Stress Testing. PLoS One. 2015;10:e0138474.
[xi] Hanratty CG, Koyama Y, Rasmussen HH, Nelson GI, Hansen PS, Ward MR. Exaggeration of nonculprit stenosis severity during acute myocardial infarction: implications for immediate multivessel revascularization. J Am Coll Cardiol. 2002;40:911-6.
[xii] Toma M, Buller CE, Westerhout CM, Fu Y, O'Neill WW, Holmes DR Jr, Hamm CW, Granger CB, Armstrong PW; APEX-AMI Investigators. Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: insights from the APEX-AMI trial. Eur Heart J. 2010;31:1701-7.
Authors: Peter Ong, Udo SechtemHospital Robert Bosch KrankenhausDepartment of CardiologyStuttgart, Germany
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