バルサルタンはアジア人の高血圧患者に有益性をもたらす

KYOTO HEART Study：バルサルタンは高リスクの日本人高血圧患者の罹患率および死亡率を減少させる
KYOTO HEART Study: Valsartan reduces morbidity and mortality in Japanese patients with high risk hypertension
KYOTO HEARTスタディの結果、従来の高血圧治療にアンジオテンシン受容体拮抗薬（ARB）バルサルタンを追加することにより日本人の心血管イベントの高リスク高血圧患者の心血管予後が改善することが示された、とESC 2009ホットラインセッションで発表され同時にEuropean Heart Journalオンライン版に掲載された。しかし、2つの治療群間の血圧に有意差はなく、この有益性は降圧効果のみでは説明できないことが示唆された。3.000人以上の日本人患者（女性43%、平均年齢66歳）をバルサルタン追加群またはARB以外の降圧剤使用群に無作為に割り付けた。全ての患者が血圧コントロール不良であり、心血管リスクファクターを1つ以上有していた。バルサルタン群において明確な有益性が認められたため、このスタディは3.27年の観察期間中央値の後早期に終了した。ARB以外の治療群と比較し、バルサルタン群においては、心血管または脳血管イベントを発症した患者が有意に少なかった（83人対155人；HR 0.55、95%CI 0.42～072、p=0.00001)。この一次エンドポイント発現率の有意差は、主に狭心症（22件対44件；HR 0.51、95%CI 0.31～0.86、p=0.01） および脳卒中/一過性脳虚血発作（25件対46件；HR 0.55、95%CI 0.34～0.89、p<0.05）の発現が少ないことによるものであった。
Full Text

The KYOTO HEART Study, which took place in Japan between January 2004 and January 2009, shows that the addition of valsartan to conventional antihypertensive treatment to improve blood pressure control is associated with an improved cardiovascular outcome in Japanese hypertensive patients at high risk of CVD events.

It remains to be determined whether the evidence found in Western countries for the benefit of blockade of the renin-angiotensin system could be directly applied in East Asian populations as a long-term strategy. The KYOTO HEART Study was designed to investigate the add-on effect of valsartan (an angiotensin II receptor antagonist, ARB) versus non-ARB optimal antihypertensive treatment on cardiovascular morbidity and mortality in Japanese hypertensive patients with uncontrolled blood pressure and high cardiovascular risks.

The KYOTO HEART Study was a multicentre, prospective, randomized comparison study with a response-dependent dose titration scheme. More than 3000 Japanese patients were assessed for eligibility (43% female, mean age 66 years); all had uncontrolled hypertension and one or more cardiovascular risk factors (such as diabetes, smoking habit, lipid metabolism abnormality, a history of ischemic heart disease, cerebrovascular disease or peripheral arterial occlusive disease, obesity (BMI>25) and left ventricular hypertrophy on electrocardiogram). 3031 patients were randomized to receive either additional treatment with valsartan or non-ARB conventional therapies.

The primary endpoint was a composite of defined cardio- or cerebrovascular events such as stroke/transient ischemic attack, myocardial infarction, hospitalization for heart failure, hospitalization for angina pectoris, aortic dissection, lower limb arterial obstruction, emergency thrombosis, transition to dialysis, or doubling of serum creatinine levels.

The study was prematurely stopped after a median observation time of 3.27 years. This was for ethical reasons because of unequivocal benefit in the valsartan group.

  • Compared with non-ARB arm, fewer individuals in the valsartan arm reached a primary endpoint (83 vs. 155; HR 0.55, 95% CI 0.42-072, p=0.00001). This difference in primary endpoint rate was mainly attributable to reduced incidences of angina pectoris (22 vs. 44; HR 0.51,95% CI 0.31-0.86, p=0.01), stroke/TIA (25 vs. 46; HR 0.55, 95% CI 0.34-0.89, p<0.05).
  • Differences in acute myocardial infarction (7 vs. 11), heart failure (12 vs. 26), arteriosclerosis obliterance (11 vs. 12), and aortic dissection (3 vs. 5) were not significant. In addition, rates of all-cause mortality (22 in valsartan arm vs. 32 in non-ARB arm) and cardiovascular mortality (8 vs. 13) were not significant.
  • Blood pressure at baseline was 157/88 mmHg in the both groups. Mean blood pressure during the treatment period was 133.1/76.1 mmHg in the valsartan add-on arm and 133.3/76.0 mmHg in the non-ARB arm.

ays principal investigator Professor Hiroaki Matsubara, "The KYOTO HEART Study was first designed to evaluate whether the addition of valsartan to conventional antihypertensive treatment to improve blood pressure control influences the cardiovascular outcome in Japanese high-risk hypertensive patients. The study showed that valsartan has the additional benefits of cardiovascular event prevention for hypertensive patients in East Asia with metabolic syndrome or high-risks."