유럽심장학회 연례학술회의에서 엔트레스토^® 신장 관련 연구결과 발표 신장 관련 복합사건 감소 및 신기능 악화 지연 확인¹

• PARAGLIIDE-HF와 PARAGON-HF 추가 분석 연구에서 엔트레스토 치료가 심부전 환자의 신기능에 긍정적인 혜택 줄 수 있음을 확인¹
• 급성/만성, 입원/외래 관계없이 심박출률 40% 초과 심부전 환자에서 엔트레스토 치료 이후 신장 관련 복합사건 감소, eGFR 감소 속도 완화¹

한국노바티스(대표이사 사장 유병재)는 8월 25일부터 28일까지 열린 유럽심장학회 연례학술회의(ESC Congress 2023)에서 노바티스의 심부전 치료제 엔트레스토(성분명 발사르틴/사쿠비트릴)의 신장 관련한 혜택을 확인한 PARAGLIIDE-HF와 PARAGON-HF의 추가적인 통합 분석 연구결과가 발표됐다고 5일 밝혔다.

PARAGLIDE-HF 와 PARAGON-HF는 다기관, 이중 맹검, 무작위 배정, 대조 연구로, 좌심실 박출률이 40%를 초과하는 심부전 환자를 대상으로 엔트레스토와 발사르탄 단독요법 간의 안전성 및 내약성을 비교 분석한 연구다.

하버드의대 브리검 여성병원(Brigham and Women’s Hospital Harvard Medical School)의 무티아 바두가나단(Muthiah Vaduganathan) 박사가 발표한 이번 연구에서는 두 연구에 참여한 총 5,262명(PARAGLIDE-HF 466명, PARAGON-HF 4,796명)의 심부전 환자를 대상으로 신장 관련 복합사건(기준점 대비 eGFR(사구체여과율) 50% 이상 감소, 말기신부전, 신장 관련 사망)과 eGFR 감소 폭을 분석했다.

심장과 신장은 심혈관 기능의 안정적인 유지를 위해 유기적인 관계를 갖고 상호작용하므로 심부전 환자에게는 신장 기능의 저하가 동반되지만, ARB, MRA, SGLT-2 억제제 등 기존의 심부전 치료제들은 좌심실 박출률이 40%를 초과하는 심부전 환자에서 신장 관련한 혜택을 확인하지 못했다.¹

이번 연구 결과에서 엔트레스토 투여군은 대조군(발사르탄 단독요법) 대비 급성 심부전으로 입원한 환자와 외래 치료를 받는 환자 모두에서 임상적으로 신장 관련 복합사건을 감소시키는 것으로 나타났다. 치료 시작 후 2개월(58일)만에 통계적으로 유의한 효과가 관찰되기 시작해 2년 동안 유지됐다. 2년 간의 추적 관찰 결과 엔트레스토 투여군의 100환자년(Patient-years) 당 신장 관련 복합사건 발생은 0.8건(95% CI 0.7-1.1)으로 대조군의 1.4건(95% CI 1.2-1.7)보다 낮았다. 대조군 대비 엔트레스토 투여군의 신장 관련 복합사건 발생 위험비(Hazard Ratio) 역시 0.60(95% CI 0.44-0.83, P=0.002)으로 낮게 나타났다. 개별적인 사건 발생 수를 살펴보면 엔트레스토 투여군과 대조군에서 각각 기준점 대비 eGFR(사구체여과율) 50% 이상 감소 60건 vs. 99건, 말기신부전 27건 vs. 34건, 신장 관련 사망 1건 vs. 3건이었다. 이러한 효과는 좌심실 박출률(60% 이하/60% 초과) 및 eGFR(60mL/min/1.73m2 이상/이하)과 무관하게 모든 주요 하위그룹에서 공통적으로 나타났다.¹

더불어, 엔트레스토는 시간 경과에 따른 eGFR의 감소 폭도 완화시킨다는 점이 확인됐다. 엔트레스토 투여군과 대조군 간 연간 eGFR 감소 폭은 PARAGON-HF에서 0.6mL/min/1.73m2(95% CI 0.4-8.0, P=0.030), PARAGLIDE-HF에서 4.2mL/min/1.73m2(95% CI 0.3-0.8, P<0.001)의 차이가 유지됐다.¹

무티아 박사는 “이번 연구를 통해 엔트레스토는 발사르탄 단독요법 대비 급성 및 만성, 입원 및 외래 환자에 관계없이 좌심실 박출율 40% 초과 심부전 환자의 신장 관련 사건의 위험을 줄일 수 있을 뿐만 아니라, 심부전 환자의 유병기간 동안 eGFR 감소 속도를 완화하는 효과까지 확인됐다”고 말했다.

한국노바티스 희귀질환 및 심혈관 사업부 총괄 조연진 전무는 “심장과 신장 기능의 악화는 서로에게 악영향을 미치고, 동시에 두 장기의 질환이 동반되는 경우 예후가 더욱 나쁜 것으로 알려져 있어 심부전 환자들은 신기능에 각별히 주의를 기울여야 한다”고 강조하며, “이번 연구 결과를 바탕으로 심부전 환자들이 심장기능 뿐 아니라 신기능 개선을 기대하면서 치료받을 수 있을 수 있을 것이라 기대된다”고 밝혔다. 또한 “앞으로도 한국노바티스는 심부전 환자들이 조기에 엔트레스토 치료를 통해 사망 및 입원을 줄일 수 있도록 꾸준히 노력할 것”이라고 덧붙였다.

엔트레스토는 전례 없는 안지오텐신 수용체-네프릴리신 억제제(ARNI) 계열 치료제이자 심장에 직접 작용하는 혁신 신약이다.^2-6 ARNI는 두 가지 경로로 심장 신경 호르몬에 작용하며, 심혈관계에 이로운 NP 신경 호르몬은 활성화하는 동시에 심혈관계에 해로운 RAAS는 억제한다.⁷ 엔트레스토는 좌심실 수축기능이 정상보다 낮은 만성 심부전 환자(NYHA class II-IV)에서 심혈관 질환으로 인한 사망 및 심부전으로 인한 입원 위험성 감소에 허가되었으며,⁸ 2022년 국내 심부전 진료 지침에서 심부전을 처음 진단받은 환자 및 기존 RAAS억제제를 사용하지 않았던 환자를 포함한 모든 심박출률 저하 심부전 환자에서 초기부터 사용되어야 하는 약제로 권고됐다.⁹

심부전의 증상과 구분, 치료 가이드라인

심부전은 심장이 펌프질을 하지 못하여 신체로 충분한 혈액을 보내지 못하는 상태로 심장 질환의 가장 마지막 단계를 의미한다. 또한 고령에서 유병률이 급격히 증가하는 대표적인 질환이다. 연령으로 볼 때 60세 미만에선 전체 인구의 1% 정도지만 80세 이상에선 그 비중이 12.6%를 넘는다.10 주요 증상은 ▲누웠을 때 유독 숨쉬기가 힘든 경우 ▲휴식 시 또는 수면 중에 갑자기 호흡곤란이 발생할 경우 ▲기침이 밤에 심해지는 증상 등 호흡과 관련된 증상으로 심부전을 의심해 볼 수 있다.11

심부전은 심장이 박동할 때마다 좌심실에서 나오는 혈액의 비율로 심장이 얼마나 혈액을 잘 공급하고 있는지 알려주는 지표인 박출률에 따라 ▲박출률 감소 심부전과 ▲정상 심박출률 미만 심부전으로 분류한다.1^2-14국내 박출률 지표 별 환자는 심박출률 감소 심부전이 전체 환자의 약 58%, 정상 심박출률 미만 심부전이 전체 환자의 약 30% 등이다.1⁵

심부전 치료와 관련 국내외 가이드라인에서는 엔트레스토를 표준 치료제로 권고하고 있다. 2022년 7월 개정된 국내 심부전 진료지침 (Korean Society of Heart Failure, KSHF) 에서는 엔트레스토를 초기 치료로 ARB 또는 ACE억제제보다 우선하여 고려할 것을 권고했다.⁹ 또한 2022년 4월, 미국심장학회(American College of Cardiology, ACC) 심부전 가이드라인에서도 엔트레스토를 심박출률 감소 심부전 환자의 ‘초기 최우선’ 치료제로 권장했으며 기존에 심부전 기본 치료제로 사용되던 ARB 혹은 ACE 억제제보다도 우선 고려할 수 있도록 개정됐다.¹⁶ 2021년 8월 개정된 유럽심장학회(European Society of Cardiology, ESC) 심부전 가이드라인에서도 ARNI 계열(엔트레스토) 등 심부전 사망률을 낮추는 4가지 필수 약제를 동시에 시작하는 복합적 치료 전략을 강조했다.¹⁷

노바티스(Novartis)에 대하여

노바티스는 인류의 생명 연장과 삶의 질 개선을 목표로 의약품 혁신에 매진하는 세계적인 제약 기업이다. 최첨단 과학기술과 디지털 기술을 접목하여 사회와 환자가 필요로 하는 혁신적인 의약품 개발에 앞장서고 있으며, 매년 세계에서 R&D에 가장 많은 투자를 하는 기업 순위에 이름을 올리고 있다. 노바티스의 의약품으로 치료받는 인구는 전 세계적으로 약 10억여명에 달하며 최신 의약품에 대한 환자 접근성을 높이는 혁신적인 방안들을 도입하고자 하는 노바티스의 노력은 현재도 계속되고 있다. 전 세계 155개국에 진출해 있으며 약 10만 명의 노바티스 임직원들이 근무하고 있다. 보다 자세한 내용은 www.novartis.com에서 확인할 수 있다.

한국노바티스(Novartis Korea)에 대하여

세계적인 제약•바이오기업, 노바티스의 한국법인이다. 현재 약 500여 명의 임직원들이 한국노바티스(www.novartis.co.kr)에서 근무하고 있으며 암, 면역, 심혈관대사, 세포 • 유전자치료, 중추신경, 안과 등의 분야에서 혁신적인 신약을 신속히 도입, 공급함으로써 한국인들의 생명연장과 치료결과, 삶의 질 개선을 위해 노력하고 있다. 한국노바티스는 최근 10년간 국내 의약품 임상시험 승인건수 1위(글로벌 제약사 부문, 2011~2020)와 국내 의약품 특허등재 건수 1위(국내외 제약사 전체, 2021년 기준)를 차지하며 혁신적인 신약개발 및 공급을 위해 국내 이해관계자와 활발히 협력하고 있다. 이 밖에도 바이오 및 디지털 헬스 분야의 우수기업을 발굴하고 지원하기 위해 ‘헬스엑스 챌린지 서울’, ‘오픈 이노베이션 챌린지’ 등 국내 헬스케어 산업의 발전에 이바지하기 위한 노력을 경주하고 있다. 대표적인 사회공헌 프로그램으로는 희귀 난치성 환자 및 가족들의 정서적 안정을 돕는 ‘치유(CHEER YOU)’ 등이 있다. 보다 자세한 내용은 www.novartis.co.kr에서 확인할 수 있다.

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