Use of antithrombotic therapy for secondary prevention in patients with stable atherosclerotic cardiovascular disease: Insights from the COordinated National Network to Engage Cardiologists in the antithrombotic Treatment of patients with CardioVascular Disease (CONNECT-CVD) study.

BACKGROUND: Although acetylsalicylic acid is the most commonly used antithrombotic agent for the secondary prevention of cardiovascular events, residual atherothrombotic risk has prompted a guideline recommendation for the addition of dual antiplatelet therapy (DAPT) or dual pathway inhibition (DPI) in high vascular risk patients. Accordingly, the CONNECT CVD quality enhancement initiative provides a contemporary "snapshot" of the clinical features and antithrombotic management of atherosclerotic cardiovascular disease (ASCVD) patients in Canada. METHODS: Canadian cardiologists (49 cardiologists from six provinces) undertook a retrospective chart audit of 10 ASCVD patients in their outpatient practice who met the Cardiovascular Outcomes for People Using Anticoagulation Strategy-like criteria from May 2018 to April 2019. RESULTS: Of the 492 (two cardiologists provided 11 patients) enroled, average age was 70 years, 25% were female, 39% had diabetes and 20% had atrial fibrillation. Prior revascularisation was common (percutaneous coronary artery intervention 61%, coronary artery bypass graft 39%), with 31% having multivessel disease. A total of 47% of patients had a Reduction of Atherothrombosis for Continued Health bleeding score of ≥11 (~2.8% risk of serious bleeding at 2 years). Single antiplatelet therapy (SAPT) alone was most commonly used (62%), while 22% were on DAPT alone. In total, 22% were on oral anticoagulation (OAC), with 16% being on non-vitamin K oral anticoagulant alone, 5% on DPI and 1% received triple therapy. CONCLUSIONS: In contemporary Canadian clinical practice of stable ASCVD patients, a large number of patients receive antithrombotic therapy other than SAPT. Further efforts are required to guide the appropriate selection of patients in whom more potent antithrombotic therapies may safely reduce residual risk.

Comparative efficacy of aliskiren monotherapy and ramipril monotherapy in patients with stage 2 systolic hypertension: subgroup analysis of a double-blind, active comparator trial.

Aliskiren is the first direct renin inhibitor approved for the treatment of hypertension. Blood pressure (BP) control in stage 2 hypertension with aliskiren monotherapy has not been reported. This was a post hoc analysis of the subgroup of patients with stage 2 systolic hypertension (baseline mean sitting systolic BP [msSBP]≥160 mmHg) who completed the 12-week monotherapy phase of a 6-month, double-blind, randomized study. A total of 175 patients were randomized to aliskiren 150 mg (n = 88) or ramipril 5 mg (n = 87) with optional up-titration to aliskiren 300 mg or ramipril 10 mg, respectively, at weeks 6 and 12. In the subgroup of patients with stage 2 systolic hypertension, aliskiren lowered msSBP and mean sitting diastolic BP (msDBP) by 22.3/12.7 mmHg from baseline to week 12; compared with a reduction of 18.1/10.2 mmHg with ramipril. The maximum BP reductions achieved with aliskiren were 60.0/34.0 mmHg (from a baseline of 172.7/107.3 mmHg). Aliskiren was noninferior (P < 0.0001) to ramipril for SBP reduction with nonsignificant superiority (P = 0.052), and superior (P = 0.043) to ramipril for DBP reduction. The proportion of patients who achieved BP control (<140/90 mmHg) after 12 weeks of monotherapy was larger with aliskiren (34/88, 38.6%) than with ramipril (22/87, 25.3%; P = 0.038). In this post hoc analysis, 12 weeks of monotherapy with aliskiren 150-300 mg provided effective mean BP reductions (22/13 mmHg) and was superior to ramipril 5-10 mg in controlling BP in patients with stage 2 systolic hypertension.

Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during long-term (6 months) treatment and withdrawal in patients with hypertension.

INTRODUCTION: This subgroup analysis assessed the effects of treatment based on the direct renin inhibitor, aliskiren, or the angiotensin-converting enzyme inhibitor, ramipril, on plasma renin activity (PRA), plasma renin concentration (PRC) and other biomarkers in a 26-week randomised, double-blind trial. Changes in PRA and PRC after stopping treatment were also assessed. METHODS: After placebo run-in, 842 patients (mean sitting diastolic blood pressure (BP) 95-109 mmHg) were randomised to aliskiren 150 mg or ramipril 5 mg. Dose titration and hydrochlorothiazide addition were allowed after Week 6 and 12, respectively, for inadequate BP control. Patients completing active treatment were re-randomised to current regimen or placebo during a 4-week posttreatment phase. RESULTS: BP reductions were independent of baseline PRA at Week 12, were greater with aliskiren- than ramipril-based therapy at Week 26 (17.9/13.3 vs. 15.2/12.0 mmHg, p<0.05) and persisted for longer after stopping aliskiren. Aliskiren-based therapy reduced geometric mean PRA (-63%, p<0.05; n=103), while ramipril-based therapy increased PRA (+143%, p<0.05; n=100) at Week 26; PRC increased in both groups (aliskiren: +224% [n=33], ramipril: +145% [n=39], both p<0.05). Four weeks after stopping aliskiren-based therapy, PRA remained 52% below pre-treatment baseline; PRA returned to baseline 2 weeks after stopping ramipril-based therapy. CONCLUSIONS: Aliskiren-based therapy produced sustained BP and PRA reductions over 26 weeks; ramipril-based therapy lowered BP and increased PRA. PRA reductions persisted 4 weeks after stopping aliskiren, suggesting an inhibitory effect beyond the elimination half-life of the drug.

Comparative efficacy and safety of aliskiren, an oral direct renin inhibitor, and ramipril in hypertension: a 6-month, randomized, double-blind trial.

OBJECTIVES: This double-blind study compared long-term efficacy, safety and tolerability of the oral direct renin inhibitor aliskiren and the angiotensin-converting enzyme inhibitor ramipril alone and combined with hydrochlorothiazide in patients with hypertension. METHODS: After a 2-4-week placebo run-in, 842 patients [mean sitting diastolic blood pressure (msDBP) 95-109 mmHg] were randomized to aliskiren 150 mg (n = 420) or ramipril 5 mg (n = 422). Dose titration (to aliskiren 300 mg/ramipril 10 mg) and subsequent hydrochlorothiazide addition (12.5 mg, titrated to 25 mg if required) were permitted at weeks 6, 12, 18 and 21 for inadequate blood pressure control. Patients completing the 26-week active-controlled treatment period were re-randomized to their existing regimen or placebo for a 4-week double-blind withdrawal phase. RESULTS: Six hundred and eighty-seven patients (81.6%) completed the active treatment period. At week 26, aliskiren-based therapy produced greater mean reductions in mean sitting systolic blood pressure (17.9 versus 15.2 mmHg, P = 0.0036) and msDBP (13.2 versus 12.0 mmHg, P = 0.025), and higher rates of systolic blood pressure control (< 140 mmHg; 72.5 versus 64.1%, P = 0.0075) compared with ramipril-based therapy. During withdrawal, blood pressure increased more rapidly after stopping ramipril than aliskiren-based therapy; median blood pressure reached 140/90 mmHg after 1 and 4 weeks, respectively. Blood pressure reductions were maintained with continued active treatment. Aliskiren therapy was well tolerated. Overall adverse event rates were similar with aliskiren (61.3%) and ramipril (60.4%); cough was more frequent with ramipril (9.5%) than aliskiren (4.1%). CONCLUSIONS: Aliskiren-based therapy was well tolerated and produced sustained blood pressure reductions in patients with hypertension over 6 months, greater than those with ramipril-based therapy.