■ 試験デザイン
TPECOに分けると下記のようになります
T: 試験デザイン PROBE（prospective, randomized, open, blinded endpoints）
3.26年f/u
P: 対象 50歳以上の高血圧患者でCVDリスクを1つ以上持つもの
75歳以上28.2% アジア人< 2.1%
除外：糖尿病、脳卒中既往
E: 介入 厳格降圧群：目標SBP < 120 mmHg
C: 比較 標準降圧群：目標SBP < 140 mmHg
O: 結果 複合エンドポイント = 心筋梗塞、その他の急性冠症候群、脳卒中、急性非代償性心不全、心血管死
■ 結果
At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group.
この試験で気がついたところ
・ サイアザイド系降圧薬（特にクロルタリドン）が第一選択推奨されている
・ 血圧の測定方法
・有害事象について
・ サイアザイド系降圧薬（特にクロルタリドン）が第一選択推奨されている
After the participants underwent randomization, their baseline antihypertensive regimens were adjusted on the basis of the study-group assignment. The treatment algorithms were similar to those used in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.22 These algorithms and our formulary are listed in Figures S1 and S2 and Table S1 in the Supplementary Appendix. All major classes of antihypertensive agents were included in the formulary and were provided at no cost to the participants. SPRINT investigators could also prescribe other antihypertensive medications (not provided by the study). The protocol encouraged, but did not mandate, the use of drug classes with the strongest evidence for reduction in cardiovascular outcomes, including thiazide-type diuretics (encouraged as the first-line agent), loop diuretics (for participants with advanced chronic kidney disease), and beta-adrenergic blockers (for those with coronary artery disease).5,27 Chlorthalidone was encouraged as the primary thiazide-type diuretic, and amlodipine as the preferred calcium-channel blocker.28,29 Azilsartan and azilsartan combined with chlorthalidone were donated by Takeda Pharmaceuticals International and Arbor Pharmaceuticals; neither company had any other role in the study.
今回のサイアザイド系利尿剤を第一選択に勧められており、さらにその中でもクロルタリドンが推奨されております。クロルタリドンは今までのエビデンスから効果があることがわかっているのですが、残念ながら日本での発売は中止になっております。
・血圧測定方法については
Dose adjustment was based on a mean of three blood-pressure measurements at an office visit while the patient was seated and after 5 minutes of quiet rest; the measurements were made with the use of an automated measurement system (Model 907, Omron Healthcare).
受診時に会話をせずに安静座位5分後にオムロンの907自動血圧計で3回測定した平均値を用いた。とあるので、通常臨床での利用は難しいです。血圧は測定条件で変動があるので、条件の整え方で目標血圧がかわってきます。特に安静座位5分後の血圧測定に関しては、ほぼ再現は不可能だと思います。
もっとも近い条件は自宅血圧であり、現時点での自宅血圧目標は概ね135/75 mmHg未満なので、今回の結果を参考にさらに下げに行くかを判断していくことが私達の仕事です。
・有害事象について
厳格降圧目標群のほうが有害事象は多いものの、総死亡を含めた効果は厳格降圧目標群のほうが低いことを考えると、注意は払うものの、有害事象増加を理由に厳格降圧目標を避ける理由にはならないと思います。
■ 参照文献
SPRINT Research Group et al., N Engl J Med. 2015 Nov 26;373(22):2103-16.
PMID: 26551272