Hypertension management often requires escalation beyond initial monotherapy to achieve blood pressure (BP) targets, with options including dose escalation of the primary agent or addition of a secondary medication (e.g., a diuretic to an angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]). Guidelines such as those from the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) favor combination therapy for its synergistic effects and reduced adverse event risks. This review synthesizes and compares outputs from three AI models—Grok, ChatGPT, and Perplexity—generated in response to a query on the benefits of adding a secondary agent versus dose escalation. The AI responses, structured as IMRaD papers, were analyzed for consistency in efficacy, safety, adherence, and outcomes, supplemented by peer-reviewed literature to validate findings. Key comparisons reveal strong alignment on the superiority of combination therapy, with minor variations in quantitative estimates and emphasis.
| Aspect | Grok | ChatGPT | Perplexity | Combined Synthesis |
|---|---|---|---|---|
| BP Reduction | ~5x more than doubling dose; additional 5-7 mmHg SBP; faster targets (twice as many achieve goal) | 10-20 mmHg additional SBP vs. 5-7 mmHg for dose escalation | Greater and synergistic; 5x more than doubling dose | Combination yields 2-5x greater reductions (10-20 mmHg SBP) vs. dose escalation (5-7 mmHg); faster control |
| Side Effects | Fewer dose-related events; low withdrawals | Higher risk with dose escalation (e.g., bradycardia, edema); combinations minimize | Lower risk/severity; fewer metabolic issues | Reduced dose-dependent effects in combinations (e.g., electrolyte imbalances, orthostatic hypotension); better tolerability |
| Adherence & Persistence | Improved with SPCs (15% better); reduced pill burden | Not explicitly detailed; implies simplicity in regimens | Not detailed; focuses on overall tolerability | SPCs enhance adherence (up to 54% improvement); higher persistence in combinations |
| Clinical Outcomes | Reduced CV events; no increased MACE | Reduced stroke/MI/HF; better organ protection | Superior vs. monotherapy for stroke/HF/mortality | Improved CV protection (e.g., 13-17% better BP control linked to lower events); renal/LVH benefits |
This synthesis integrated outputs from Grok, ChatGPT, and Perplexity, each formatted as IMRaD reviews based on the query. Outputs were parsed for key themes (BP efficacy, side effects, adherence, outcomes) and quantitatively compared. Discrepancies were validated against peer-reviewed sources identified via web searches using terms like "meta-analysis combination therapy vs dose escalation hypertension benefits." Inclusion criteria: RCTs, meta-analyses, or guidelines published 2010-2025 with quantitative data on BP reductions, adverse events, or outcomes (n=500 where applicable). Exclusion: Non-peer-reviewed or non-hypertension-focused studies. Data extraction emphasized pooled estimates; narrative synthesis highlighted AI consistencies and contrasts. No primary data; 10 sources selected for relevance.
The table above compares the AI outputs and provides a combined synthesis. All AIs emphasized combination therapy's superiority, drawing from meta-analyses showing additive BP effects (e.g., 10-20 mmHg SBP reductions) versus diminishing returns from dose escalation (5-7 mmHg). Grok provided the most detailed quantitative data, including RCTs like ACCOMPLISH (6-8 mmHg additional SBP) and a 2023 meta-analysis (7.4 mmHg greater SBP reduction). ChatGPT highlighted mechanistic synergy (e.g., diuretics + RAAS blockers) and trial examples (ASCOT-BPLA: 5-10 mmHg). Perplexity focused on overall efficacy (5x BP drop) and CV protection, citing trials like ALLHAT.
Side effects were consistently lower in combinations due to reduced doses, with AIs noting offsets (e.g., ARB mitigating diuretic-induced hypokalemia). Adherence was a strength in Grok (15-54% improvement with SPCs), less emphasized elsewhere. Outcomes favored combinations for CV risk reduction (e.g., stroke, heart failure), with Grok and Perplexity quantifying benefits (e.g., 40% higher control rates).
Cross-validation: Meta-analyses confirm ~5-fold greater BP lowering with combinations versus doubling doses , with improved adherence (RR 2.1 for persistence) and lower costs ($1,357/year savings) .
The AI outputs show strong concordance: all conclude combination therapy outperforms dose escalation in BP control, tolerability, and outcomes, aligning with evidence from meta-analyses (e.g., 5-fold efficacy multiplier) . Grok's detailed table and recent citations (e.g., 2023 JAMA Cardiol) provide the most rigorous synthesis, while ChatGPT emphasizes mechanisms and Perplexity highlights metabolic protections—complementary perspectives without major conflicts. Variations include BP estimates (Grok/ChatGPT: 5-7 mmHg for escalation; Perplexity: plateauing benefits) and adherence focus (stronger in Grok).
Evidence supports these: combinations achieve 10-20 mmHg SBP reductions versus 5-7 mmHg for escalation , with fewer adverse events (e.g., 13% lower risk) . SPCs enhance adherence (8-14% higher MPR) and reduce CV events (e.g., 17% better control) . Limitations: AI outputs cite older trials (e.g., 2002 ALLHAT) ; heterogeneity in populations. Future research: Long-term RCTs in diverse cohorts. Clinically, prioritize combinations (e.g., ACEI + diuretic) for most, per 2017 ACC/AHA guidelines .