Insights from Dr. Shigeru Saito: Decrease in PCI volume and Effient (Prasugrel) proper dosing

Today I was scanning the PCI literature from Japan, and I was reading Dr. Shigeru Saito’s blog. I admire Dr. Saito’s work. I first met him at St. Vincent’s Hospital in NYC as a young attending and I saw how he opened impossible chronic total occlusions in the coronaries, prior to the day of retrograde techniques. I used to scan his blogs for case pearls: how to use Corsairs, how to do parallel wires, etc. And he used to post beautiful pictures of different cath labs from over the world. As a budding young cardiologist in NYC, reading his blog gave me motivation to work harder to hone my PCI techniques. I learned how to do transradial PCI by reading his blog.

But alas, he stopped posting on his site. And I got busy, and I stopped following his posts.

In my recent trip to japan, I went to a regular bookstore and I was surprised to find a book on FFR on the bookshelf!

IMG_9535

Two things I learned from Dr. Saito from his site:

(1) Effient dose should be lowered to 3.75 mg po qd for Asians: the FDA approved dose is too high.

Shigeru Saito, M.D, Vice Director, Director of Cardiology and Catheterization Laboratories at Shonan Kamakura General Hospital said, “The PRASFIT-ACS trial was the largest phase 3 comparative clinical trial conducted in ACS-PCI patients in Japan. In a Japanese phase 2 clinical study prasugrel 20 mg LD/ 3.75 mg MD provided consistent and potent platelet inhibition. [i] Based on this result prasugrel 20 mg LD/ 3.75 mg MD was the selected dose for conducting PRASFIT-ACS clinical study.  As a result, the fact that the incidence rate of cardiovascular events in prasugrel patients was 9.4 percent, while 11.8 percent in clopidogrel patients and its risk reduction was 23 percent, and the fact that no difference in bleeding tendency between both groups are very meaningful for patients undergoing PCI from a clinical standpoint in Japan. Now that the PRASFIT-ACS has shown a consistent trend in terms of efficacy results to the TRITON-TIMI38 study and at the dose studied in PRASFIT-ACS, similar tolerability was shown compared to clopidogrel for Japanese ACS-PCI patients. I expect prasugrel to become a standard therapeutic drug for ACS-PCI treatment in Japan.”

[Note: The indicated dose for prasugrel in the outside of Japan is 60mg LD and 10mg MD]

(2) Bio-absorbable scaffold and TAVI are big in Japan.

(3) In Japan, PCI numbers have decreased, just like in US. The reasons are similar to those in US: aggressive primary and secondary prevention, DES, and use of FFR. (COURAGE trial I am sure also has a role, though he did not discuss this.)

PCI症例数が伸び悩んでいる要因としてはいくつか考えられます。その最大の要因は、優れた薬剤溶出性ステント (Drug-Eluting Stent: DES)の出現でしょう。非薬剤溶出性ステント (Bare-Metal Stent: BMS)の時代と比較して明らかにステント内再狭窄 (In-Stent Restenosis: ISR)の発生頻度が低下していますので、繰り返して PCIを受けねばならない患者さんは減少しました。第一世代の DES (CYPHERやTAXUS)に比較しても現在臨床の現場において、通常診療の中で用いられている DES (Xience-Xpedition, Promus-Element, Resolute-Integrity, Nobori)は難しい病変に対しても明らかに再狭窄低減効果を示しています。総合的に、この DESの進化により、再治療の必要性は 大きく低下しました。また当科では、数多くの新しい DESの治験を行っておりますが、これらの新しい改良された DESにおいては、さらに良好な成績が期待されます。

次に大きな要因として挙げられるのは、一次予防と二次予防の徹底ということが考えられます。一次予防というのは、冠動脈病変発症前から、虚血性心疾患を促進すると考えられる因子を除去することです。つまり、いわゆる冠危険因子として挙げられる、高血圧症、高脂血症、糖尿病、高尿酸血症などに対して、早期から介入 (治療)を開始することです。もちろん、これらの臨床的疾病の治療のみならず、生活習慣の改善 (禁煙の徹底、日常的な適度な運動や、適正な体重コントロールなどなど)も重要です。これらの一次予防により、虚血性心疾患の発症そのものが抑制されてきています。また、冠動脈病変による疾病が発症した後でも、薬剤や生活習慣への介入により、有効な二次予防が徹底されてきています。これにより虚血性心疾患の再発率も低下してきています。

さらに臨床現場心臓カテーテル室では、FFR (Fractional Flow Reserve: 冠血流予備量比 とか 心筋血流量予備比 とか訳される)を測定することにより、今までは造影の結果、PCIが必要と考えられていた病変に対しても、生理学的にPCIが必要無い、との判断が下され、その結果 PCIを行わない (Deferred PCI)場合も多くなってきています。これによりやはり PCI症例数の頭打ちに直面しています。

I think related to this question is whether CTO PCI really helps the patients.  Bradley Strauss et al. wrote a good article on this subject in JACC last year (J Am Coll Cardiol. 2014;64(12):1281-1289.  doi:10.1016/j.jacc.2014.06.1181). One of the most contentious issue is how safe is retrograde PCI technique for CTO, and I am citing from his paper:

The highly experienced, dedicated European CTO PCI operators who contributed to the ERCTO registry reported a higher complication rate with the retrograde approach. Coronary perforation occurred in 4.7% of procedures, compared with 2.1% in the anterograde approach (p = 0.04). Retrograde approach procedures were longer, with higher fluoroscopy times and larger contrast load administration, and were associated with increased rates of non–Q-wave MI at 30 days, (2.1% vs. 1%; p = 0.08) . A meta-analysis of 3,482 patients from 26 studies who underwent a retrograde approach reported an overall success rate of 83.3%, lower than non-CTO PCI. Major adverse cardiac event (MACE) rates (0.7% death, 0.7% urgent CABG, 3.1% MI, and 0.5% stroke) with the retrograde approach were low, although collateral vessel perforations were still common (6.9%), with 4.3% coronary perforation and 1.4% cardiac tamponade. 

As to the benefit of CTO PCI, this paragraph from the paper summarizes the current status:

Many studies and several meta-analyses compared patient outcomes with successful and failed PCI CTO, consistently finding improved outcomes with successful procedures. Khan et al. 61 evaluated 23 observational studies comparing clinical outcomes between patients with successful CTO recanalization and those managed conservatively as a result of failed PCI. Successful CTO PCI was significantly associated with improved all-cause mortality (relative risk: 0.54), and lower MACE rates (relative risk: 0.70) (61). Similarly, a meta-analysis of 13 observational studies found that, compared with unsuccessful PCI, successful PCI is associated with improved mortality and reduced need for CABG 62. These studies (and the majority of studies cited in this review) are observational and are thus prone to confounding. There is a lack of robust type A evidence with hard clinical outcomes on the benefits of CTO revascularization. Several trials expected to advance these discussions are currently underway or in advanced planning stages. The EXPLORE (Evaluating Xience V and LV function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction) trial, a randomized study in the final enrollment stages, addresses whether revascularization of a CTO nonculprit artery in patients presenting with ST-segment elevation MI will be beneficial for LV function at 4 months. DECISION-CTO (Drug-Eluting Stent Implantation versus Optimal Medical Treatment in Patients with Chronic Total Occlusion) is a randomized trial to compare the long-term (3-year) outcome of drug-eluting stent implantation with optimal medical treatment. EURO-CTO (European Study on the Utilization of Revascularization vs. Optimal Medical Therapy for the Treatment of Chronic Total Coronary Occlusions) is a multicenter trial to evaluate 1- and 3-year outcomes and assess QOL in patients randomized to revascularization or optimal medical therapy.

There is more to this paper. But because of such uncertainty, CTO PCI has become much more limited, leading to decrease in procedural volume in Japan as well as in US.

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