Upstream clopidogrel, prasugrel, or ticagrelor for patients treated with primary angioplasty: Results of an angiographic randomized pilot study.

OBJETIVES: The main objective of the present randomized pilot study was to explore the effects of upstream prasugrel or ticagrelor or clopidogrel for patients with ST-segment-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: Administration of clopidogrel "as soon as possible" has been advocated for STEMI. Pretreatment with prasugrel and ticagrelor may improve reperfusion. Currently, the angiographic effects of upstream administration of these agents are poorly understood. METHODS: A total of 132 patients with STEMI within the first 12 hr of chest pain referred to primary angioplasty were randomized to upstream clopidogrel (600 mg), prasugrel (60 mg), or ticagrelor (180 mg) while still in the emergency room. All patients underwent protocol-mandated thrombus aspiration. RESULTS: Macroscopic thrombus material was retrieved in 79.5% of the clopidogrel group, 65.9% of the prasugrel group, and 54.3% of the ticagrelor group (P = 0.041). At baseline angiography, large thrombus burden was 97.7% vs. 87.8% vs. 80.4% in the clopidogrel, prasugrel, and ticagrelor groups, respectively (P = 0.036). Also, at baseline, 97.7% presented with an occluded target vessel in the clopidogrel group, 87.8% in the prasugrel group and 78.3% in the ticagrelor group (P = 0.019). At the end of the procedure, the percentages of patients with combined TIMI grade III flow and myocardial blush grade III were 52.3% for clopidogrel, 80.5% for prasugrel, and 67.4% for ticagrelor (P = 0.022). CONCLUSIONS: In patients with STEMI undergoing primary PCI within 12 hr, upstream clopidogrel, prasugrel or ticagrelor have varying angiographic findings, with a trend toward better results for the latter two agents. © 2015 Wiley Periodicals, Inc.

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment).

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434.